PTCH1 (Protein patched homolog 1) variants and mutations
PTCH1 (also known as Protein patched homolog 1) is a human protein-coding gene encoding a protein patched homolog 1 protein. It suppresses Smoothened in the absence of Hedgehog ligands and thereby keeps Hedgehog developmental signaling inactive until an appropriate signal is received. Germline loss-of-function variants cause Gorlin syndrome, while somatic pathway activation drives basal-cell carcinoma and other tumors. This analysis covers 5,949 PTCH1 variants and mutations. Of these, 49% have computational variant effect predictions. Disease context includes nevoid basal cell carcinoma syndrome, holoprosencephaly, and basal cell carcinoma. Example PTCH1 variants include A2V, S3A, and S3L.
Variant analysis overview
- Gene: PTCH1
- Protein: Protein patched homolog 1
- UniProt accession: Q13635
- Organism: Homo sapiens
- Variants analyzed: 5949
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 5,706 unspecified-consequence records; 4 in-frame deletions; 55 missense variants; 162 synonymous variants; 10 frameshift variants; 4 stop-gained variants; 2 in-frame insertions; 3 splice-region variants; 3 substitution
- Prediction scores: 2,944 variants have prediction scores (49% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: nevoid basal cell carcinoma syndrome, holoprosencephaly, basal cell carcinoma, medulloblastoma, Inherited cancer-predisposing syndrome, hereditary neoplastic syndrome, Abnormality of the skeletal system, hereditary disease, major depressive disorder, intelligence, osteoarthritis, hip, pilocytic astrocytoma.
Protein structure and variant hotspots
- Protein features: 12 transmembrane segments; 1 domains; 8 post-translational modification sites.
- Structural context: 991 variants have structural context.
- PTM context: 32 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable PTCH1 variants
Examples include A2V, S3A, S3L, S3T, S3W, A4G, A4T, A4V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2V (p.Ala2Val), rs1843916565, ClinGen CA374121793, ClinVar RCV001043879, ClinVar RCV002355009, REVEL 0.45, CADD 24.10, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- S3A (p.Ser3Ala), rs2118910766, ClinGen CA374121778, ClinVar RCV002037139, Ensembl rs2118910766, AlphaMissense 0.13, MetaLR 0.75, Uncertain significance, Gorlin syndrome
- S3L (p.Ser3Leu), rs1587701230, ClinGen CA374121774, ClinVar RCV001340545, Ensembl rs1587701230, REVEL 0.53, AlphaMissense 0.35, Uncertain significance, Gorlin syndrome
- S3T (p.Ser3Thr), rs2118910766, ClinGen CA374121782, ClinVar RCV001929891, Ensembl rs2118910766, AlphaMissense 0.13, MetaLR 0.75, Uncertain significance, Gorlin syndrome
- S3W (p.Ser3Trp), rs1587701230, ClinGen CA374121772, ClinVar RCV000809029, Ensembl rs1587701230, AlphaMissense 0.35, MetaLR 0.76, Uncertain significance, Gorlin syndrome
- A4G (p.Ala4Gly), rs540045689, ClinGen CA16612694, ClinVar RCV000463891, ClinVar RCV001169520, REVEL 0.33, CADD 21.80, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- A4T (p.Ala4Thr), rs2538404922, ClinGen CA374121766, ClinVar RCV003609374, REVEL 0.34, CADD 23.60, Uncertain significance, Gorlin syndrome
- A4V (p.Ala4Val), rs540045689, ClinGen CA374121752, ClinVar RCV000796321, ClinVar RCV006274030, REVEL 0.31, CADD 23.50, Uncertain significance, not specified; Gorlin syndrome
- G5A (p.Gly5Ala), rs864622762, ClinGen CA347992, ClinVar RCV000203690, ClinVar RCV002390556, REVEL 0.34, CADD 15.30, Likely benign
- G5D (p.Gly5Asp), rs864622762, ClinGen CA374121745, ClinVar RCV003878779, REVEL 0.33, CADD 20.80, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- G5S (p.Gly5Ser), rs1843915589, ClinGen CA374121750, ClinVar RCV001322149, ClinVar RCV004809563, AlphaMissense 0.12, MetaLR 0.38, Uncertain significance, not provided; Gorlin syndrome
- N6D (p.Asn6Asp), rs1587701202, ClinGen CA374121734, ClinVar RCV000806251, ClinVar RCV002397641, AlphaMissense 0.09, MetaLR 0.34, Conflicting interpretations, Gorlin syndrome; Holoprosencephaly 7; Basal cell nevus syndrome 1
- N6K (p.Asn6Lys), rs878853848, ClinGen CA374121722, ClinVar RCV001305200, ClinVar RCV004944983, REVEL 0.20, CADD 22.20, Uncertain significance, Gorlin syndrome
- N6Y (p.Asn6Tyr), rs1587701202, ClinGen CA374121737, ClinVar RCV002406297, AlphaMissense 0.09, MetaLR 0.34, Uncertain significance, Hereditary cancer-predisposing syndrome
- A7G (p.Ala7Gly), rs1564092028, ClinGen CA374121705, ClinVar RCV000701353, ClinVar RCV003432744, REVEL 0.30, CADD 22.10, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Gorlin syndrome
- A7P (p.Ala7Pro), TOPMed rs1843914764, Uncertain significance, Hereditary cancer-predisposing syndrome
- A7T (p.Ala7Thr), TOPMed rs1843914764, REVEL 0.28, CADD 20.70, Uncertain significance, Gorlin syndrome
- A7V (p.Ala7Val), rs1564092028, ClinGen CA374121702, ClinVar RCV000697946, ClinVar RCV002422546, REVEL 0.22, CADD 14.70, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome; Basal cell carcinoma, sus
- A8S (p.Ala8Ser), rs2118910390, ClinGen CA374121669, ClinVar RCV002013294, Ensembl rs2118910390, REVEL 0.26, CADD 17.80, Uncertain significance, Gorlin syndrome
- A8T (p.Ala8Thr), rs2118910390, ClinGen CA374121666, ClinVar RCV001897418, Ensembl rs2118910390, REVEL 0.24, CADD 21.30, Uncertain significance, Gorlin syndrome
- A8V (p.Ala8Val), rs1843914282, ClinGen CA374121663, ClinVar RCV001062389, Ensembl rs1843914282, REVEL 0.26, CADD 22.30, Uncertain significance, Gorlin syndrome
- E9D (p.Glu9Asp), rs1354741081, ClinGen CA374121638, ClinVar RCV002441576, gnomAD rs1354741081, REVEL 0.23, CADD 17.90, Uncertain significance, Hereditary cancer-predisposing syndrome
- E9G (p.Glu9Gly), Ensembl rs1843913965, Uncertain significance, Hereditary cancer-predisposing syndrome
- E9K (p.Glu9Lys), rs1843914121, ClinGen CA374121660, ClinVar RCV001037419, ClinVar RCV003283878, REVEL 0.21, CADD 22.60, Conflicting interpretations, Gorlin syndrome; Hereditary cancer-predisposing syndrome; Basal cell carcinoma
- P10A (p.Pro10Ala), rs1587701162, ClinGen CA374121632, ClinVar RCV001041013, ClinVar RCV002436549, REVEL 0.20, CADD 19.00, Conflicting interpretations, Gorlin syndrome; Hereditary cancer-predisposing syndrome
- P10L (p.Pro10Leu), rs1046883730, ClinGen CA196555787, ClinVar RCV003368214, ClinVar RCV005103988, REVEL 0.23, CADD 22.80, Uncertain significance, Hereditary cancer-predisposing syndrome
- P10R (p.Pro10Arg), TOPMed rs1046883730, REVEL 0.19, CADD 22.60, Uncertain significance, Hereditary cancer-predisposing syndrome
- P10S (p.Pro10Ser), rs1587701162, ClinGen CA374121635, ClinVar RCV001016910, ClinVar RCV001819729, REVEL 0.22, CADD 20.70, Conflicting interpretations, not specified; Hereditary cancer-predisposing syndrome; Gorlin syndrome
- Q11H (p.Gln11His), rs1320203029, ClinGen CA374121606, ClinVar RCV001043054, ClinVar RCV002451165, REVEL 0.31, CADD 19.10, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- Q11K (p.Gln11Lys), rs2538404666, ClinGen CA374121621, ClinVar RCV003608788, REVEL 0.19, CADD 20.90, Uncertain significance, Gorlin syndrome
- Q11R (p.Gln11Arg), rs2538404656, ClinGen CA374121612, ClinVar RCV003296222, ClinVar RCV004823142, REVEL 0.22, CADD 16.90, Conflicting interpretations, not provided; Hereditary cancer-predisposing syndrome
- D12A (p.Asp12Ala), Ensembl rs2118910194
- D12E (p.Asp12Glu), rs1057522533, ClinGen CA374121589, ClinVar RCV000800780, ClinVar RCV002345787, REVEL 0.27, CADD 12.30, Uncertain significance, Gorlin syndrome
- D12N (p.Asp12Asn), rs2538404636, ClinGen CA374121600, ClinVar RCV003382204, Uncertain significance, Hereditary cancer-predisposing syndrome
- D12Y (p.Asp12Tyr), rs2538404636, ClinGen CA374121599, ClinVar RCV002337534, REVEL 0.22, CADD 21.70, Likely benign, Hereditary cancer-predisposing syndrome
- R13C (p.Arg13Cys), rs779791579, ClinGen CA374121580, ClinVar RCV001195974, ClinVar RCV002365895, REVEL 0.23, CADD 22.50, Uncertain significance, Hereditary cancer-predisposing syndrome; Basal cell carcinoma, susceptibility to
- R13G (p.Arg13Gly), rs779791579, ClinGen CA334329, ClinVar RCV000168136, ClinVar RCV000388546, REVEL 0.26, CADD 16.00, Benign
- R13H (p.Arg13His), rs1843911577, ClinGen CA374121577, ClinVar RCV001313461, Ensembl rs1843911577, REVEL 0.19, CADD 16.70, Uncertain significance, Gorlin syndrome
- R13L (p.Arg13Leu), Ensembl rs1843911577, REVEL 0.21, CADD 16.20, Uncertain significance
- R13P (p.Arg13Pro), Ensembl rs1843911577, Uncertain significance
- R13S (p.Arg13Ser), rs779791579, ClinGen CA374121584, ClinVar RCV003080054, REVEL 0.23, CADD 14.70, Uncertain significance, Gorlin syndrome
- G14D (p.Gly14Asp), rs1564091998, ClinGen CA374121563, ClinVar RCV000686375, ClinVar RCV003303111, REVEL 0.24, CADD 12.80, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- G14S (p.Gly14Ser), rs1233426743, ClinGen CA374121568, ClinVar RCV000628335, ClinVar RCV001021870, REVEL 0.29, CADD 14.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Gorlin syndrome
- G15A (p.Gly15Ala), Ensembl rs2118910016
- G15D (p.Gly15Asp), Ensembl rs2118910016, REVEL 0.24, CADD 13.20, Uncertain significance, Gorlin syndrome
- G15S (p.Gly15Ser), rs1240000266, ClinGen CA374121556, ClinVar RCV001059885, TOPMed rs1240000266, REVEL 0.28, CADD 12.00, Uncertain significance, PTCH1-related disorder; Gorlin syndrome; Hereditary cancer-predisposing syndrome
- G16A (p.Gly16Ala), Ensembl rs1843909922, Uncertain significance
- G16C (p.Gly16Cys), TOPMed rs1057515721, gnomAD rs1057515721, REVEL 0.31, CADD 18.00, Uncertain significance
- G16D (p.Gly16Asp), rs1843909922, ClinGen CA374121537, ClinVar RCV001214140, ClinVar RCV004944882, REVEL 0.34, CADD 10.40, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- G16R (p.Gly16Arg), TOPMed rs1057515721, gnomAD rs1057515721, Uncertain significance
- G16S (p.Gly16Ser), rs1057515721, ClinGen CA10634607, ClinVar RCV000269791, ClinVar RCV000327144, REVEL 0.16, CADD 12.20, Benign
- G16V (p.Gly16Val), Ensembl rs1843909922, REVEL 0.27, CADD 15.10, Uncertain significance
- G17D (p.Gly17Asp), rs1265021279, ClinGen CA374121519, ClinVar RCV002335988, ClinVar RCV006470807, REVEL 0.23, CADD 15.80, Uncertain significance, Gorlin syndrome; Hereditary cancer-predisposing syndrome
- G17R (p.Gly17Arg), rs1217844666, ClinGen CA374121526, ClinVar RCV001023390, ClinVar RCV004761878, AlphaMissense 0.25, MetaLR 0.45, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- G17S (p.Gly17Ser), TOPMed rs1217844666, gnomAD rs1217844666, REVEL 0.18, AlphaMissense 0.25, Likely benign, Hereditary cancer-predisposing syndrome
- G17V (p.Gly17Val), TOPMed rs1265021279, gnomAD rs1265021279, REVEL 0.17, CADD 16.80, Uncertain significance
- S18C (p.Ser18Cys), rs1199437529, ClinGen CA374121511, ClinVar RCV002655028, TOPMed rs1199437529, REVEL 0.24, CADD 16.10, Benign, Gorlin syndrome
- S18G (p.Ser18Gly), rs1199437529, ClinGen CA374121512, ClinVar RCV000817190, ClinVar RCV001023886, REVEL 0.29, CADD 10.80, Uncertain significance, Gorlin syndrome
- S18I (p.Ser18Ile), rs750062220, ClinGen CA374121509, ClinVar RCV002815349, ClinVar RCV004946061, AlphaMissense 0.09, MetaLR 0.44, Uncertain significance, Gorlin syndrome; Hereditary cancer-predisposing syndrome
- S18R (p.Ser18Arg), rs1328705680, ClinGen CA374121508, ClinVar RCV002351626, ClinVar RCV006559056, REVEL 0.21, CADD 16.50, Uncertain significance, Gorlin syndrome; Hereditary cancer-predisposing syndrome
- S18T (p.Ser18Thr), ExAC rs750062220, gnomAD rs750062220, REVEL 0.18, AlphaMissense 0.09
- G19A (p.Gly19Ala), rs587780708, ClinGen CA374121503, ClinVar RCV003075577, ClinVar RCV004673790, REVEL 0.27, CADD 16.30, Uncertain significance, Gorlin syndrome; Hereditary cancer-predisposing syndrome
- G19C (p.Gly19Cys), rs778460384, ClinGen CA374121505, ClinVar RCV003382202, REVEL 0.37, CADD 22.80, Uncertain significance, Hereditary cancer-predisposing syndrome
- G19D (p.Gly19Asp), rs587780708, ClinGen CA374121504, ClinVar RCV001024426, ClinVar RCV001064996, REVEL 0.36, CADD 17.60, Conflicting interpretations, Gorlin syndrome; Hereditary cancer-predisposing syndrome; not provided
- G19R (p.Gly19Arg), ExAC rs778460384, TOPMed rs778460384, gnomAD rs778460384, Likely benign
- G19S (p.Gly19Ser), rs778460384, ClinGen CA5139065, ClinVar RCV000761070, ClinVar RCV000828033, REVEL 0.19, CADD 15.00, Conflicting interpretations, Neuroblastoma; Hereditary cancer-predisposing syndrome; not provided
- G19V (p.Gly19Val), rs587780708, ClinGen CA332592, ClinVar RCV000123041, ClinVar RCV000484179, REVEL 0.35, CADD 21.30, Benign
- C20G (p.Cys20Gly), rs1843905982, ClinGen CA374121500, ClinVar RCV002355707, AlphaMissense 0.07, MetaLR 0.29, Uncertain significance, Hereditary cancer-predisposing syndrome
- C20S (p.Cys20Ser), rs1420016285, ClinGen CA374121498, ClinVar RCV002635774, ClinVar RCV004946026, REVEL 0.19, CADD 14.50, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- C20W (p.Cys20Trp), Ensembl rs1843905199
- I21F (p.Ile21Phe), ExAC rs756724967, TOPMed rs756724967, gnomAD rs756724967, Benign
- I21L (p.Ile21Leu), rs756724967, ClinGen CA5139064, ClinVar RCV000458640, ClinVar RCV001024995, REVEL 0.24, CADD 11.20, Benign, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- I21M (p.Ile21Met), rs1284183739, ClinGen CA374121489, ClinVar RCV001321074, ClinVar RCV002259103, REVEL 0.22, CADD 15.90, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Gorlin syndrome
- I21N (p.Ile21Asn), rs1843904837, ClinGen CA374121491, ClinVar RCV001234337, ClinVar RCV004659427, REVEL 0.26, CADD 14.90, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- I21S (p.Ile21Ser), Ensembl rs1843904837, Uncertain significance
- I21V (p.Ile21Val), rs756724967, ClinGen CA374121494, ClinVar RCV001916535, ExAC rs756724967, REVEL 0.20, CADD 8.92, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- G22A (p.Gly22Ala), 1000Genomes rs575700967, ExAC rs575700967, REVEL 0.23, AlphaMissense 0.11, Uncertain significance
- G22C (p.Gly22Cys), gnomAD rs1843904468, REVEL 0.26, CADD 20.90, Uncertain significance
- G22D (p.Gly22Asp), 1000Genomes rs575700967, ExAC rs575700967, REVEL 0.27, AlphaMissense 0.11, Uncertain significance, Hereditary cancer-predisposing syndrome
- G22R (p.Gly22Arg), gnomAD rs1843904468, Uncertain significance, Hereditary cancer-predisposing syndrome
- G22S (p.Gly22Ser), rs1843904468, ClinGen CA374121488, ClinVar RCV003296230, gnomAD rs1843904468, REVEL 0.20, CADD 17.60, Uncertain significance, Hereditary cancer-predisposing syndrome
- G22V (p.Gly22Val), rs575700967, ClinGen CA374121484, ClinVar RCV002050146, ClinVar RCV005262543, AlphaMissense 0.11, MetaLR 0.46, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- A23D (p.Ala23Asp), rs761204245, ClinGen CA5139061, ClinVar RCV001196937, ExAC rs761204245, REVEL 0.18, CADD 18.30, Uncertain significance, Basal cell carcinoma, susceptibility to, 1
- A23S (p.Ala23Ser), 1000Genomes rs863224654, TOPMed rs863224654, gnomAD rs863224654, REVEL 0.20, CADD 13.50, Uncertain significance, Hereditary cancer-predisposing syndrome
- A23T (p.Ala23Thr), rs863224654, ClinGen CA338400, ClinVar RCV000199131, ClinVar RCV001025668, REVEL 0.21, CADD 15.60, Likely benign
- A23V (p.Ala23Val), rs761204245, ClinGen CA5139062, ClinVar RCV000628480, ClinVar RCV002258974, REVEL 0.17, CADD 18.00, Conflicting interpretations, not specified; Hereditary cancer-predisposing syndrome; not provided
- P24A (p.Pro24Ala), rs1338078012, ClinGen CA374121479, ClinVar RCV002367347, TOPMed rs1338078012, AlphaMissense 0.05, MetaLR 0.45, Uncertain significance, Hereditary cancer-predisposing syndrome
- P24L (p.Pro24Leu), rs767973616, ClinGen CA5139059, ClinVar RCV000690903, ClinVar RCV002369856, REVEL 0.21, AlphaMissense 0.12, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Gorlin syndrome; not specified
- P24R (p.Pro24Arg), rs767973616, ClinGen CA374121476, ClinVar RCV001362056, ExAC rs767973616, AlphaMissense 0.12, MetaLR 0.41, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- P24S (p.Pro24Ser), rs1338078012, ClinGen CA374121478, ClinVar RCV001026036, ClinVar RCV001220944, REVEL 0.14, AlphaMissense 0.05, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Gorlin syndrome; not provided
- P24T (p.Pro24Thr), rs1338078012, ClinGen CA374121480, ClinVar RCV002367343, ClinVar RCV003502654, REVEL 0.16, AlphaMissense 0.05, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- G25A (p.Gly25Ala), rs774712511, ClinGen CA5139057, ClinVar RCV000564085, ClinVar RCV000821615, REVEL 0.21, CADD 11.40, Uncertain significance, Gorlin syndrome
- G25D (p.Gly25Asp), rs1843902347, ClinGen CA916081541, ClinVar RCV001035899, ClinVar RCV002379479, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- G25E (p.Gly25Glu), rs774712511, ClinGen CA5139058, ClinVar RCV000823669, ClinVar RCV001766753, REVEL 0.18, CADD 9.71, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Gorlin syndrome; not provided
- G25R (p.Gly25Arg), rs1843902765, ClinGen CA374121475, ClinVar RCV002903723, Ensembl rs1843902765, AlphaMissense 0.18, MetaLR 0.37, Uncertain significance, Hereditary cancer-predisposing syndrome
- G25V (p.Gly25Val), ExAC rs774712511, TOPMed rs774712511, gnomAD rs774712511, REVEL 0.20, CADD 15.20, Uncertain significance, Hereditary cancer-predisposing syndrome
- R26G (p.Arg26Gly), TOPMed rs1408427240, gnomAD rs1408427240, REVEL 0.19, CADD 19.80, Uncertain significance, Hereditary cancer-predisposing syndrome
- R26L (p.Arg26Leu), rs1181222222, ClinGen CA374121468, ClinVar RCV000809957, ClinVar RCV003166288, REVEL 0.23, CADD 20.50, Conflicting interpretations, Gorlin syndrome; Hereditary cancer-predisposing syndrome; Basal cell carcinoma
- R26P (p.Arg26Pro), TOPMed rs1181222222, gnomAD rs1181222222, REVEL 0.23, CADD 21.70, Uncertain significance, Hereditary cancer-predisposing syndrome
- R26W (p.Arg26Trp), rs1408427240, ClinGen CA374121470, ClinVar RCV000802147, ClinVar RCV001026729, REVEL 0.24, CADD 23.10, Uncertain significance, Hereditary cancer-predisposing syndrome; Basal cell carcinoma, susceptibility to
- P27A (p.Pro27Ala), rs1245076183, ClinGen CA374121465, ClinVar RCV001315156, gnomAD rs1245076183, REVEL 0.17, CADD 19.40, Uncertain significance, Gorlin syndrome
- P27L (p.Pro27Leu), rs762960154, ClinGen CA5139055, ClinVar RCV000563665, ClinVar RCV006463407, REVEL 0.21, CADD 22.30, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- P27R (p.Pro27Arg), ExAC rs762960154, gnomAD rs762960154, REVEL 0.19, CADD 22.00, Uncertain significance
- P27S (p.Pro27Ser), rs1245076183, ClinGen CA374121464, ClinVar RCV000553524, ClinVar RCV002420333, REVEL 0.16, CADD 20.60, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- A28G (p.Ala28Gly), TOPMed rs1220641430, Uncertain significance, not provided
- A28P (p.Ala28Pro), rs1341574540, ClinGen CA374121460, ClinVar RCV002430341, REVEL 0.22, CADD 20.70, Uncertain significance, Hereditary cancer-predisposing syndrome
- A28S (p.Ala28Ser), TOPMed rs1341574540, REVEL 0.20, CADD 17.40
- A28T (p.Ala28Thr), TOPMed rs1341574540, REVEL 0.17, CADD 20.80
- A28V (p.Ala28Val), rs1220641430, ClinGen CA374121456, ClinVar RCV001371563, ClinVar RCV004945097, REVEL 0.22, CADD 19.70, Conflicting interpretations, Gorlin syndrome; Hereditary cancer-predisposing syndrome
- G29A (p.Gly29Ala), rs2118909005, ClinGen CA374121451, ClinVar RCV003382218, CADD 21.60, Uncertain significance, Hereditary cancer-predisposing syndrome
- G29E (p.Gly29Glu), rs2118909005, ClinGen CA374121452, ClinVar RCV002037219, Ensembl rs2118909005, AlphaMissense 0.12, MetaLR 0.35, Uncertain significance, Gorlin syndrome
- G29R (p.Gly29Arg), rs2118909022, ClinGen CA374121453, ClinVar RCV001955221, ClinVar RCV003464264, AlphaMissense 0.16, MetaLR 0.35, Uncertain significance, Basal cell carcinoma, susceptibility to, 1; Gorlin syndrome; Hereditary cancer-p
- G30D (p.Gly30Asp), rs2538403955, ClinGen CA374121446, ClinVar RCV003310899, Uncertain significance, Hereditary cancer-predisposing syndrome
- G30S (p.Gly30Ser), gnomAD rs1843900330, REVEL 0.27, CADD 17.10
- G31E (p.Gly31Glu), rs1329331221, ClinGen CA374121440, ClinVar RCV001019134, ClinVar RCV001360062, REVEL 0.24, CADD 18.00, Benign/Likely benign, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- G31R (p.Gly31Arg), rs768512190, ClinGen CA5139053, ClinVar RCV000575799, ClinVar RCV000628426, REVEL 0.17, CADD 17.10, Conflicting interpretations, not specified; Hereditary cancer-predisposing syndrome; Gorlin syndrome
- G31W (p.Gly31Trp), ExAC rs768512190, TOPMed rs768512190, gnomAD rs768512190, Benign
- R32G (p.Arg32Gly), rs913603578, ClinGen CA196555664, ClinVar RCV001059459, ClinVar RCV002374944, REVEL 0.20, CADD 21.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- R32K (p.Arg32Lys), rs746923835, ClinGen CA374121436, ClinVar RCV001979960, ExAC rs746923835, REVEL 0.19, CADD 17.60, Uncertain significance, Gorlin syndrome
- R32M (p.Arg32Met), rs746923835, ClinGen CA374121437, ClinVar RCV003310891, REVEL 0.31, CADD 22.20, Uncertain significance, Hereditary cancer-predisposing syndrome
- R32T (p.Arg32Thr), rs746923835, ClinGen CA5139052, ClinVar RCV001373267, ClinVar RCV003298619, REVEL 0.20, CADD 18.10, Conflicting interpretations, Gorlin syndrome; Hereditary cancer-predisposing syndrome
- R32W (p.Arg32Trp), gnomAD rs913603578, Uncertain significance
- R33C (p.Arg33Cys), rs1843899190, ClinGen CA374121431, ClinVar RCV002387228, ClinVar RCV003094876, REVEL 0.43, CADD 24.70, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- R33G (p.Arg33Gly), TOPMed rs1843899190, Uncertain significance, Hereditary cancer-predisposing syndrome
- R33H (p.Arg33His), rs2118908774, ClinGen CA374121430, ClinVar RCV002387459, ClinVar RCV005601906, REVEL 0.37, AlphaMissense 0.30, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- R33L (p.Arg33Leu), rs2118908774, ClinGen CA374121428, ClinVar RCV003177310, ClinVar RCV006473861, AlphaMissense 0.30, MetaLR 0.52, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- R33P (p.Arg33Pro), Ensembl rs2118908774, Uncertain significance
- R34* (p.Arg34Ter), Ensembl rs2118908736
- R34G (p.Arg34Gly), Ensembl rs2118908736, CADD 22.90
- R34K (p.Arg34Lys), rs771847879, ClinGen CA5139050, ClinVar RCV000590878, ClinVar RCV002367995, REVEL 0.24, CADD 14.40, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- R34S (p.Arg34Ser), Ensembl rs2118908666, Likely benign
- R34T (p.Arg34Thr), rs771847879, ClinGen CA5139051, ClinVar RCV000628397, ClinVar RCV001009723, REVEL 0.23, CADD 16.10, Benign, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- R35G (p.Arg35Gly), gnomAD rs1385550193, Likely benign
- R35P (p.Arg35Pro), rs587778627, ClinGen CA374121420, ClinVar RCV003610027, ExAC rs587778627, AlphaMissense 0.25, MetaLR 0.54, Uncertain significance, Gorlin syndrome
- R35Q (p.Arg35Gln), rs587778627, ClinGen CA161658, ClinVar RCV000121883, ClinVar RCV000467292, REVEL 0.23, AlphaMissense 0.25, Benign
- R35W (p.Arg35Trp), rs1385550193, ClinGen CA374121421, ClinVar RCV001238228, ClinVar RCV004944937, REVEL 0.32, CADD 22.20, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- T36A (p.Thr36Ala), rs1843898216, ClinGen CA374121417, ClinVar RCV001305061, ClinVar RCV003365314, REVEL 0.18, CADD 15.60, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- T36M (p.Thr36Met), TOPMed rs1449765833, gnomAD rs1449765833, Uncertain significance, Hereditary cancer-predisposing syndrome
- T36P (p.Thr36Pro), rs1843898216, ClinGen CA374121418, ClinVar RCV001320551, ClinVar RCV006274189, REVEL 0.29, CADD 17.20, Uncertain significance, Gorlin syndrome; not specified
- T36R (p.Thr36Arg), rs1449765833, ClinGen CA374121414, ClinVar RCV001051483, ClinVar RCV002416388, REVEL 0.26, CADD 16.30, Conflicting interpretations, Basal cell nevus syndrome 1; Hereditary cancer-predisposing syndrome; Gorlin syn
- T36S (p.Thr36Ser), gnomAD rs1843898216, Uncertain significance, Hereditary cancer-predisposing syndrome
- G37A (p.Gly37Ala), rs748780206, ClinGen CA374121411, ClinVar RCV001017327, ClinVar RCV001205535, AlphaMissense 0.09, MetaLR 0.44, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Gorlin syndrome; Breast carcinoma
- G37E (p.Gly37Glu), rs748780206, ClinGen CA5139047, ClinVar RCV000685634, ClinVar RCV002458197, REVEL 0.25, AlphaMissense 0.09, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- G37R (p.Gly37Arg), rs199976372, ClinGen CA5139048, ClinVar RCV000228192, ClinVar RCV000328380, REVEL 0.25, CADD 18.00, Uncertain significance, Gorlin syndrome; Hereditary cancer-predisposing syndrome
- G37V (p.Gly37Val), rs748780206, ClinGen CA374121410, ClinVar RCV002428953, ClinVar RCV005058827, REVEL 0.23, AlphaMissense 0.09, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- G37W (p.Gly37Trp), rs199976372, ClinGen CA5139049, ClinVar RCV000531311, ClinVar RCV001797745, REVEL 0.31, CADD 23.20, Conflicting interpretations, not specified; not provided; Hereditary cancer-predisposing syndrome
- G38V (p.Gly38Val), rs2538403705, ClinGen CA2825001649, ClinVar RCV004523043, REVEL 0.21, CADD 13.50, Likely benign, Hereditary cancer-predisposing syndrome
- G38A (p.Gly38Ala), rs143494325, ClinGen CA350340, ClinVar RCV000206274, ClinVar RCV000569099, REVEL 0.18, CADD 11.60, Benign
- G38E (p.Gly38Glu), rs143494325, ClinGen CA339512, ClinVar RCV000200738, ClinVar RCV000492756, REVEL 0.16, CADD 12.90, Benign
- G38R (p.Gly38Arg), rs45574039, ClinGen CA196555628, ClinVar RCV000805151, ClinVar RCV005260413, REVEL 0.18, CADD 17.30, Likely benign, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- L39P (p.Leu39Pro), rs768063889, ClinGen CA5139044, ClinVar RCV002938020, ClinVar RCV003170585, REVEL 0.24, CADD 14.40, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- L39Q (p.Leu39Gln), rs768063889, ClinGen CA374121405, ClinVar RCV001926083, ClinVar RCV005465610, REVEL 0.21, CADD 13.20, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- L39R (p.Leu39Arg), ExAC rs768063889, gnomAD rs768063889, Uncertain significance
- L39V (p.Leu39Val), Ensembl rs1587700581, Likely benign
- R40C (p.Arg40Cys), rs1843895996, ClinGen CA374121403, ClinVar RCV001057199, ClinVar RCV002348420, REVEL 0.24, CADD 18.80, Uncertain significance, Gorlin syndrome; Hereditary cancer-predisposing syndrome; Basal cell carcinoma
- R40G (p.Arg40Gly), TOPMed rs1843895996, Uncertain significance
- R40H (p.Arg40His), ExAC rs755400723, gnomAD rs755400723, REVEL 0.23, AlphaMissense 0.14, Uncertain significance, not specified
- R40L (p.Arg40Leu), rs755400723, ClinGen CA374121399, ClinVar RCV001294351, ExAC rs755400723, AlphaMissense 0.14, MetaLR 0.53, Uncertain significance, Gorlin syndrome
- R40P (p.Arg40Pro), ExAC rs755400723, gnomAD rs755400723, Uncertain significance
- R41C (p.Arg41Cys), rs1554709496, ClinGen CA374121396, ClinVar RCV000559958, ClinVar RCV003159705, REVEL 0.52, AlphaMissense 0.52, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- R41G (p.Arg41Gly), rs1554709496, ClinGen CA374121397, ClinVar RCV003504036, Ensembl rs1554709496, AlphaMissense 0.52, MetaLR 0.74, Uncertain significance, Gorlin syndrome
- R41H (p.Arg41His), NCI-TCGA TCGA novel, Ensembl rs1554709493, REVEL 0.34, AlphaMissense 0.29, Uncertain significance
- R41L (p.Arg41Leu), rs1554709493, ClinGen CA374121393, ClinVar RCV000628349, ClinVar RCV006424638, AlphaMissense 0.29, MetaLR 0.74, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- R41P (p.Arg41Pro), rs1554709493, ClinGen CA374121394, ClinVar RCV002369230, ClinVar RCV003103325, AlphaMissense 0.29, MetaLR 0.74, Uncertain significance, Gorlin syndrome; Hereditary cancer-predisposing syndrome
- R41S (p.Arg41Ser), rs1554709496, ClinGen CA374121398, ClinVar RCV000699286, ClinVar RCV002352179, REVEL 0.38, AlphaMissense 0.52, Uncertain significance, Hereditary cancer-predisposing syndrome; Gorlin syndrome; Basal cell carcinoma
- A42D (p.Ala42Asp), TOPMed rs1030446889, gnomAD rs1030446889, REVEL 0.28, CADD 0.80, Likely benign
- A42G (p.Ala42Gly), rs1030446889, ClinGen CA196555548, ClinVar RCV000613176, ClinVar RCV000802616, REVEL 0.24, CADD 1.42, Benign/Likely benign, Hereditary cancer-predisposing syndrome; not specified; Gorlin syndrome
- A42P (p.Ala42Pro), rs2118908042, ClinGen CA374121391, ClinVar RCV001998600, Ensembl rs2118908042, AlphaMissense 0.08, MetaLR 0.51, Uncertain significance, Gorlin syndrome
- A42T (p.Ala42Thr), Ensembl rs2118908042, Uncertain significance
- A42V (p.Ala42Val), TOPMed rs1030446889, gnomAD rs1030446889, Likely benign
- A43G (p.Ala43Gly), Ensembl rs2118907913
- A43P (p.Ala43Pro), ExAC rs766536174, TOPMed rs766536174, gnomAD rs766536174, REVEL 0.23, CADD 13.80, Benign
- A43S (p.Ala43Ser), ExAC rs766536174, TOPMed rs766536174, gnomAD rs766536174, Benign
- A43T (p.Ala43Thr), rs766536174, ClinGen CA5139042, ClinVar RCV001324229, ClinVar RCV002384430, REVEL 0.21, CADD 8.92, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Gorlin syndrome
- A43V (p.Ala43Val), Ensembl rs2118907913, REVEL 0.24, CADD 22.40, Uncertain significance, Hereditary cancer-predisposing syndrome
- A44G (p.Ala44Gly), gnomAD rs1219886976
- A44P (p.Ala44Pro), ESP rs148863241, TOPMed rs148863241, gnomAD rs148863241, Uncertain significance
- A44T (p.Ala44Thr), ESP rs148863241, TOPMed rs148863241, gnomAD rs148863241, Uncertain significance, Hereditary cancer-predisposing syndrome
- A44V (p.Ala44Val), gnomAD rs1219886976, REVEL 0.18, CADD 19.20, Uncertain significance, Hereditary cancer-predisposing syndrome
- P45A (p.Pro45Ala), rs1843894066, ClinGen CA374121376, ClinVar RCV002387667, ClinVar RCV003464509, AlphaMissense 0.05, MetaLR 0.43, Uncertain significance, Hereditary cancer-predisposing syndrome; Basal cell carcinoma, susceptibility to
Public PTCH1 analysis runs
- PTCH1 analysis run — PTCH1 (5,949 variants) — completed 2026-08-19