MCCC1 (Q96RQ3) variants and mutations
MCCC1 (also known as Q96RQ3) is a human protein-coding gene encoding a methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial protein. It provides one subunit of mitochondrial methylcrotonyl-CoA carboxylase, an enzyme required for leucine degradation. Biallelic loss-of-function variants cause 3-methylcrotonyl-CoA carboxylase deficiency, with clinical severity ranging from asymptomatic biochemical abnormalities to metabolic decompensation. This analysis covers 1,096 MCCC1 variants and mutations. Of these, 76% have computational variant effect predictions. Disease context includes Isolated 3-methylcrotonyl-CoA carboxylase deficiency, 3-methylcrotonyl-CoA carboxylase deficiency, and hereditary disease. Example MCCC1 variants include M1T, M1V, and A2E.
Variant analysis overview
- Gene: MCCC1
- Protein: Q96RQ3
- UniProt accession: Q96RQ3
- Organism: Homo sapiens
- Variants analyzed: 1096
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 914 unspecified-consequence records; 2 stop lost; 1 stop retained variant; 69 synonymous variants; 85 missense variants; 12 frameshift variants; 5 stop-gained variants; 4 splice-region variants; 4 substitution
- Prediction scores: 833 variants have prediction scores (76% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Isolated 3-methylcrotonyl-CoA carboxylase deficiency, 3-methylcrotonyl-CoA carboxylase deficiency, hereditary disease, Parkinson disease, neurodegenerative disease, Lewy body dementia, retinitis pigmentosa, Progressive cone dystrophy, Cone rod dystrophy, early-onset non-syndromic cataract, Posterior polar cataract, congenital glaucoma.
Protein structure and variant hotspots
- Protein features: 3 domains; 6 binding sites; 5 post-translational modification sites.
- Structural context: 712 variants have structural context.
- PTM context: 6 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 MCCC1 variants
Examples include M1T, M1V, A2E, A2T, A2V, A3V, A4V, S5A. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1T (p.Met1Thr), rs776254500, ClinGen CA2719250, ClinVar RCV001377562, ClinVar RCV004746362, MetaLR 0.71, MetaSVM 0.22, Pathogenic, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- M1V (p.Met1Val), rs762463914, ClinGen CA2719251, ClinVar RCV000653495, ClinVar RCV003403504, MetaLR 0.73, MetaSVM 0.37, Uncertain significance, MCCC1-related disorder; 3-methylcrotonyl-CoA carboxylase 1 deficiency
- A2E (p.Ala2Glu), rs1260785519, ClinGen CA355324569, ClinVar RCV003109196, gnomAD rs1260785519, REVEL 0.34, CADD 22.10, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- A2T (p.Ala2Thr), gnomAD rs1460507493, REVEL 0.24, CADD 16.30
- A2V (p.Ala2Val), gnomAD rs1260785519, REVEL 0.28, CADD 19.30, Uncertain significance
- A3V (p.Ala3Val), 1000Genomes rs572765608, REVEL 0.26, CADD 19.00
- A4V (p.Ala4Val), NCI-TCGA Cosmic COSV9965, REVEL 0.28, CADD 21.50, Variant assessed as somatic; moderate impact.
- S5A (p.Ser5Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S5F (p.Ser5Phe), ExAC rs771721641, gnomAD rs771721641, REVEL 0.44, CADD 23.50
- A6T (p.Ala6Thr), TOPMed rs1157661208, gnomAD rs1157661208, REVEL 0.20, CADD 17.70
- A6V (p.Ala6Val), rs2530560582, ClinGen CA355324476, ClinVar RCV002596711, REVEL 0.24, CADD 14.70, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- V7M (p.Val7Met), TOPMed rs1718991860, REVEL 0.20, CADD 16.30
- S8W (p.Ser8Trp), TOPMed rs914177076, gnomAD rs914177076, REVEL 0.42, CADD 24.20
- V9A (p.Val9Ala), gnomAD rs1317814265
- L10P (p.Leu10Pro), TOPMed rs1718990963
- L10V (p.Leu10Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L11P (p.Leu11Pro), ExAC rs778620637, TOPMed rs778620637, gnomAD rs778620637, REVEL 0.62, CADD 25.10
- L11Q (p.Leu11Gln), ExAC rs778620637, TOPMed rs778620637, gnomAD rs778620637, REVEL 0.57, CADD 24.90
- L11V (p.Leu11Val), TOPMed rs1453383248, gnomAD rs1453383248
- A13E (p.Ala13Glu), ExAC rs757154849, TOPMed rs757154849, gnomAD rs757154849, REVEL 0.50, CADD 20.80
- A13V (p.Ala13Val), ExAC rs757154849, TOPMed rs757154849, gnomAD rs757154849, REVEL 0.39, CADD 18.00, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- A14S (p.Ala14Ser), TOPMed rs931841236, gnomAD rs931841236, REVEL 0.35, CADD 14.90
- E15K (p.Glu15Lys), rs988784745, ClinGen CA88712121, ClinVar RCV002675856, Ensembl rs988784745, REVEL 0.40, CADD 22.30, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- R16K (p.Arg16Lys), ExAC rs753835386, TOPMed rs753835386, gnomAD rs753835386, REVEL 0.26, CADD 16.10
- R16T (p.Arg16Thr), ExAC rs753835386, TOPMed rs753835386, gnomAD rs753835386, REVEL 0.52, CADD 16.20
- N17K (p.Asn17Lys), 1000Genomes rs557695078, ExAC rs557695078, TOPMed rs557695078, gnomAD rs557695078, REVEL 0.27, CADD 20.40, Likely benign
- R18G (p.Arg18Gly), gnomAD rs1443414652, REVEL 0.48, CADD 23.30
- R18P (p.Arg18Pro), 1000Genomes rs539353622, ExAC rs539353622, gnomAD rs539353622, REVEL 0.52, CADD 19.50
- R18Q (p.Arg18Gln), 1000Genomes rs539353622, ExAC rs539353622, gnomAD rs539353622, REVEL 0.23, CADD 15.40
- R18W (p.Arg18Trp), gnomAD rs1443414652, REVEL 0.47, CADD 25.30
- W19C (p.Trp19Cys), gnomAD rs1180041673, REVEL 0.52, CADD 26.40
- H20R (p.His20Arg), rs751663186, ClinGen CA2719239, ClinVar RCV001916693, ExAC rs751663186, REVEL 0.38, CADD 17.90, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- H20Y (p.His20Tyr), TOPMed rs1718987210, REVEL 0.30, CADD 21.40
- R21P (p.Arg21Pro), gnomAD rs1204217115, REVEL 0.53, CADD 25.40
- R21S (p.Arg21Ser), ExAC rs766657375, gnomAD rs766657375, REVEL 0.51, CADD 24.60
- L22F (p.Leu22Phe), gnomAD rs1490855504, REVEL 0.34, CADD 21.90
- L22P (p.Leu22Pro), TOPMed rs1718986032, REVEL 0.47, CADD 25.20
- P23L (p.Pro23Leu), rs1293019202, ClinGen CA355324201, ClinVar RCV002578378, TOPMed rs1293019202, REVEL 0.27, CADD 22.60, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- P23S (p.Pro23Ser), TOPMed rs1718985567, REVEL 0.26, CADD 20.50
- S24R (p.Ser24Arg), ExAC rs763642722, TOPMed rs763642722, gnomAD rs763642722, REVEL 0.38, CADD 13.80, Uncertain significance, not provided
- S24T (p.Ser24Thr), rs762409158, ClinGen CA2719234, ClinVar RCV001325208, ClinVar RCV004035151, REVEL 0.26, CADD 13.60, Uncertain significance, Inborn genetic diseases; 3-methylcrotonyl-CoA carboxylase 1 deficiency
- L27P (p.Leu27Pro), TOPMed rs1297847007, gnomAD rs1297847007, REVEL 0.58, CADD 23.40
- P28L (p.Pro28Leu), rs1164035251, ClinGen CA355324120, ClinVar RCV000804071, TOPMed rs1164035251, REVEL 0.38, CADD 22.30, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- P28S (p.Pro28Ser), ExAC rs774954839, TOPMed rs774954839, gnomAD rs774954839, REVEL 0.40, CADD 15.70, Uncertain significance, Inborn genetic diseases; not provided
- P29Q (p.Pro29Gln), gnomAD rs1718982873, REVEL 0.36, CADD 22.60
- P29S (p.Pro29Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R30M (p.Arg30Met), TOPMed rs976406300, REVEL 0.48, CADD 33.00
- W32* (p.Trp32Ter), rs536755857, NCI-TCGA Cosmic COSV5560, Ensembl rs536755857, CADD 34.00, Variant assessed as somatic; high impact.
- W32R (p.Trp32Arg), ExAC rs761132865, gnomAD rs761132865, REVEL 0.59, CADD 22.30
- W32S (p.Trp32Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- W34* (p.Trp34Ter), TOPMed rs985721226
- W34R (p.Trp34Arg), Ensembl rs2108569952, REVEL 0.66, CADD 21.10
- Q36K (p.Gln36Lys), Ensembl rs1577367776
- R37T (p.Arg37Thr), TOPMed rs1260217814, gnomAD rs1260217814
- M39I (p.Met39Ile), rs1718606011, ClinGen CA355322502, ClinVar RCV002994713, TOPMed rs1718606011, AlphaMissense 0.15, MetaLR 0.74, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- M39R (p.Met39Arg), ExAC rs775030303, TOPMed rs775030303, gnomAD rs775030303
- K40E (p.Lys40Glu), rs985721226, []
- Y41* (p.Tyr41Ter), rs2108569910, ClinGen CA355322442, ClinVar RCV001382304, Ensembl rs2108569910, Pathogenic
- Y41H (p.Tyr41His), ExAC rs766999178, TOPMed rs766999178, gnomAD rs766999178
- T42A (p.Thr42Ala), ExAC rs773887269, gnomAD rs773887269, REVEL 0.26, CADD 0.11
- T42I (p.Thr42Ile), TOPMed rs1222631013, gnomAD rs1222631013, REVEL 0.20, CADD 13.80
- T42P (p.Thr42Pro), ExAC rs773887269, gnomAD rs773887269, REVEL 0.27, CADD 4.08
- T42S (p.Thr42Ser), ExAC rs773887269, gnomAD rs773887269, REVEL 0.20, CADD 0.08
- T43A (p.Thr43Ala), ExAC rs201427541, gnomAD rs201427541, REVEL 0.19, CADD 11.90
- T43P (p.Thr43Pro), ExAC rs201427541, gnomAD rs201427541, REVEL 0.42, CADD 17.40
- A44F (p.Ala44Phe), rs1553868919, ClinGen CA658657354, ClinVar RCV000530709, ClinVar RCV002275089, Uncertain significance, Inborn genetic diseases; not provided; 3-methylcrotonyl-CoA carboxylase 1 defici
- A44S (p.Ala44Ser), rs201216516, ClinGen CA2719206, ClinVar RCV001144093, ClinVar RCV002557071, REVEL 0.25, CADD 4.96, Uncertain significance, not provided; 3-methylcrotonyl-CoA carboxylase 1 deficiency; Inborn genetic dise
- A44T (p.Ala44Thr), 1000Genomes rs201216516, ExAC rs201216516, TOPMed rs201216516, gnomAD rs201216516, REVEL 0.28, CADD 2.63, Uncertain significance
- A44V (p.Ala44Val), 1000Genomes rs200673204, ExAC rs200673204, TOPMed rs200673204, gnomAD rs200673204, REVEL 0.24, CADD 20.60, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency; Inborn genetic diseases; not prov
- T45A (p.Thr45Ala), TOPMed rs1718602978
- T45I (p.Thr45Ile), TOPMed rs1410294013, gnomAD rs1410294013, REVEL 0.27, CADD 25.20, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- G46E (p.Gly46Glu), rs199517715, ClinGen CA312679, ClinVar RCV000185992, ClinVar RCV000554762, REVEL 0.42, CADD 24.90, Conflicting interpretations, Inborn genetic diseases; Methylcrotonyl-CoA carboxylase deficiency; not provided
- R47G (p.Arg47Gly), rs142664377, ClinGen CA2719188, ClinVar RCV002283285, ClinVar RCV003096355, REVEL 0.27, CADD 17.10, Uncertain significance, not provided; 3-methylcrotonyl-CoA carboxylase 1 deficiency; Inborn genetic dise
- N48S (p.Asn48Ser), TOPMed rs1718443596
- I49F (p.Ile49Phe), 1000Genomes rs539670122, ExAC rs539670122, gnomAD rs539670122, REVEL 0.60, CADD 23.80
- I49T (p.Ile49Thr), ExAC rs761796928
- T50I (p.Thr50Ile), ExAC rs772126862, gnomAD rs772126862, REVEL 0.56, CADD 21.60
- T50S (p.Thr50Ser), ExAC rs772126862, gnomAD rs772126862, REVEL 0.27, CADD 18.00
- K51E (p.Lys51Glu), rs2530510970, ClinGen CA355321905, ClinVar RCV003204730, REVEL 0.92, CADD 28.60, Uncertain significance, Inborn genetic diseases
- V52L (p.Val52Leu), ExAC rs779230714, gnomAD rs779230714
- I54M (p.Ile54Met), TOPMed rs1718440391
- I54T (p.Ile54Thr), rs796051987, ClinGen CA312683, ClinVar RCV001361105, TOPMed rs796051987, REVEL 0.97, CADD 26.70, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- I54V (p.Ile54Val), gnomAD rs1183107033, REVEL 0.30, CADD 16.80
- N56K (p.Asn56Lys), rs1057520695, ClinGen CA16604839, ClinVar RCV000441741, ClinVar RCV003330667, REVEL 0.88, CADD 25.20, Conflicting interpretations, not specified; not provided
- N56S (p.Asn56Ser), ExAC rs778265702, gnomAD rs778265702
- R57G (p.Arg57Gly), TOPMed rs1718439233, REVEL 0.89, CADD 24.90
- R57K (p.Arg57Lys), rs2530510608, ClinGen CA355321821, ClinVar RCV003839046, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- R57S (p.Arg57Ser), gnomAD rs1275408389, REVEL 0.91, CADD 27.20
- G58A (p.Gly58Ala), gnomAD rs1560281232, REVEL 0.97, CADD 26.20
- E59* (p.Glu59Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E59G (p.Glu59Gly), rs2530510478, ClinGen CA355321790, ClinVar RCV003498208, Likely pathogenic, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- I60T (p.Ile60Thr), Ensembl rs1718438227
- C62Y (p.Cys62Tyr), gnomAD rs1249484909, REVEL 0.95, CADD 25.90, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- R63K (p.Arg63Lys), rs2108565998, ClinGen CA355321736, ClinVar RCV001892307, Ensembl rs2108565998, AlphaMissense 0.45, MetaLR 0.95, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- V64G (p.Val64Gly), Ensembl rs868460209
- V64M (p.Val64Met), TOPMed rs1335066204
- M65I (p.Met65Ile), cosmic curated COSV55609, gnomAD rs1337114466, REVEL 0.31, CADD 6.31
- M65L (p.Met65Leu), rs1718436080, UniProt VAR 072488, Ensembl rs1718436080, REVEL 0.55, CADD 23.50, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- M65T (p.Met65Thr), ExAC rs781578883, TOPMed rs781578883, gnomAD rs781578883, REVEL 0.74, CADD 23.40
- R66C (p.Arg66Cys), rs754460336, ClinGen CA2719171, NCI-TCGA Cosmic COSV9966, cosmic curated COSV99660, REVEL 0.91, CADD 27.30, Likely pathogenic, Methylcrotonyl-CoA carboxylase deficiency; 3-methylcrotonyl-CoA carboxylase 1 de
- R66H (p.Arg66His), rs569042803, ClinGen CA2719170, NCI-TCGA Cosmic COSV5560, cosmic curated COSV55607, REVEL 0.83, CADD 25.00, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- R66L (p.Arg66Leu), 1000Genomes rs569042803, ExAC rs569042803, TOPMed rs569042803, gnomAD rs569042803, REVEL 0.86, CADD 25.50, Uncertain significance
- T67I (p.Thr67Ile), rs2108565928, ClinGen CA355321704, ClinVar RCV001961276, Ensembl rs2108565928, REVEL 0.94, CADD 27.10, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- A68T (p.Ala68Thr), gnomAD rs1718434637, REVEL 0.83, CADD 25.20
- K69* (p.Lys69Ter), rs147741073, ClinGen CA275186, ClinVar RCV000177314, ESP rs147741073, AlphaMissense 0.17, MetaLR 0.91, Pathogenic
- K69E (p.Lys69Glu), rs147741073, ClinVar RCV004586312, ClinVar RCV005610697, ESP rs147741073, AlphaMissense 0.17, MetaLR 0.91, Uncertain significance, not specified
- K70E (p.Lys70Glu), rs750133436, ClinGen CA2719167, ClinVar RCV001277566, ClinVar RCV001880230, REVEL 0.51, CADD 26.50, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- K70N (p.Lys70Asn), 1000Genomes rs550313698, ExAC rs550313698, gnomAD rs550313698, NCI-TCGA TCGA novel, REVEL 0.44, CADD 20.20, Variant assessed as somatic; high impact.
- K70T (p.Lys70Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G72A (p.Gly72Ala), rs761521333, ClinGen CA2719165, ClinVar RCV001922865, ExAC rs761521333, REVEL 0.93, CADD 24.20, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- Q74* (p.Gln74Ter), rs1162953685, ClinGen CA355321667, cosmic curated COSV10584, ClinVar RCV002576507, CADD 36.00, Pathogenic
- Q74H (p.Gln74His), Ensembl rs1227361314, REVEL 0.61, CADD 23.50
- Q74P (p.Gln74Pro), rs2530509631, ClinGen CA2580616015, ClinVar RCV003324207, REVEL 0.74, CADD 23.30, Uncertain significance, not specified
- T75A (p.Thr75Ala), rs2530509602, ClinGen CA355321661, ClinVar RCV002466781, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- T75I (p.Thr75Ile), Ensembl rs1017964907
- V76M (p.Val76Met), gnomAD rs1234746635, REVEL 0.82, CADD 25.00
- A77E (p.Ala77Glu), ExAC rs776594363, TOPMed rs776594363, gnomAD rs776594363, Uncertain significance
- A77V (p.Ala77Val), rs776594363, ClinGen CA2719164, NCI-TCGA Cosmic COSV5560, cosmic curated COSV55606, REVEL 0.93, CADD 27.50, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- V78G (p.Val78Gly), Ensembl rs201580317
- Y79C (p.Tyr79Cys), UniProt VAR 077284, REVEL 0.95, CADD 26.30, Pathogenic, in MCC1D
- S80N (p.Ser80Asn), rs774565207, ClinGen CA2719161, ClinVar RCV000625892, ClinVar RCV002529767, REVEL 0.85, CADD 25.00, Uncertain significance, not provided; 3-methylcrotonyl-CoA carboxylase 1 deficiency; Inborn genetic dise
- S80T (p.Ser80Thr), ExAC rs774565207, TOPMed rs774565207, gnomAD rs774565207, Uncertain significance
- E81V (p.Glu81Val), TOPMed rs1280574361
- A82G (p.Ala82Gly), rs1577363370, ClinGen CA355321613, ClinVar RCV000797633, Ensembl rs1577363370, AlphaMissense 0.22, MetaLR 0.96, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- D83H (p.Asp83His), rs1485157465, ClinGen CA355321610, ClinVar RCV001301558, TOPMed rs1485157465, AlphaMissense 0.48, MetaLR 0.95, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- D83N (p.Asp83Asn), TOPMed rs1485157465, Uncertain significance
- D83Y (p.Asp83Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R84K (p.Arg84Lys), NCI-TCGA Cosmic COSV5560, cosmic curated COSV55608, Variant assessed as somatic; moderate impact.
- N85D (p.Asn85Asp), TOPMed rs1208373817, gnomAD rs1208373817, REVEL 0.31, CADD 22.00
- N85T (p.Asn85Thr), rs148616219, ClinGen CA2719160, ClinVar RCV000865064, ClinVar RCV003328637, REVEL 0.51, CADD 24.10, Conflicting interpretations, not provided; 3-methylcrotonyl-CoA carboxylase 1 deficiency
- S86C (p.Ser86Cys), ExAC rs749460045, TOPMed rs749460045, gnomAD rs749460045, REVEL 0.88, CADD 29.30
- S86P (p.Ser86Pro), rs2108565751, ClinGen CA355321568, ClinVar RCV001366749, Ensembl rs2108565751, AlphaMissense 0.81, MetaLR 0.97, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- M87L (p.Met87Leu), TOPMed rs1214601221, gnomAD rs1214601221, REVEL 0.34, CADD 17.20
- M87R (p.Met87Arg), rs2530508950, ClinGen CA355321549, ClinVar RCV002810517, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- M87V (p.Met87Val), TOPMed rs1214601221, gnomAD rs1214601221, REVEL 0.69, CADD 23.50
- H88P (p.His88Pro), TOPMed rs1352224093, gnomAD rs1352224093, REVEL 0.96, CADD 26.90, Uncertain significance
- H88R (p.His88Arg), rs1352224093, ClinGen CA355321537, ClinVar RCV001918453, TOPMed rs1352224093, REVEL 0.93, CADD 25.90, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- H88Y (p.His88Tyr), rs778145370, ClinGen CA2719158, ClinVar RCV001971840, ExAC rs778145370, REVEL 0.94, CADD 31.00, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- M91I (p.Met91Ile), NCI-TCGA TCGA novel, REVEL 0.79, CADD 34.00, Variant assessed as somatic; moderate impact.
- M91K (p.Met91Lys), gnomAD rs1333663197, Uncertain significance
- M91T (p.Met91Thr), rs1333663197, ClinGen CA355321494, ClinVar RCV001306025, gnomAD rs1333663197, REVEL 0.92, CADD 31.00, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- M91V (p.Met91Val), 1000Genomes rs2108565697, REVEL 0.81, CADD 27.90
- D93G (p.Asp93Gly), TOPMed rs1717925545
- D93Y (p.Asp93Tyr), ExAC rs765426351, gnomAD rs765426351
- E94K (p.Glu94Lys), rs1717925328, ClinGen CA355319654, NCI-TCGA Cosmic COSV5561, cosmic curated COSV55610, AlphaMissense 0.13, MetaLR 0.96, Conflicting interpretations, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- A95G (p.Ala95Gly), Ensembl rs1717924789, REVEL 0.88, CADD 26.70
- A95T (p.Ala95Thr), gnomAD rs1453501166, REVEL 0.88, CADD 26.50, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- Y96* (p.Tyr96Ter), rs1012193526, ClinGen CA355319594, ClinVar RCV002470112, ClinVar RCV003600440, Pathogenic
- Y96H (p.Tyr96His), cosmic curated COSV55606, ExAC rs761930069, TOPMed rs761930069, gnomAD rs761930069, REVEL 0.61, CADD 22.60, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency; not provided
- I98T (p.Ile98Thr), Ensembl rs2108553710, REVEL 0.91, CADD 24.50
- G99R (p.Gly99Arg), ESP rs375244642, ExAC rs375244642, TOPMed rs375244642, gnomAD rs375244642, REVEL 0.96, CADD 24.50, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- G99S (p.Gly99Ser), ESP rs375244642, ExAC rs375244642, TOPMed rs375244642, gnomAD rs375244642, REVEL 0.91, CADD 24.30, Conflicting interpretations, not specified; 3-methylcrotonyl-CoA carboxylase 1 deficiency
- P100R (p.Pro100Arg), TOPMed rs1717923164, REVEL 0.81, CADD 24.50
- A101D (p.Ala101Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A101T (p.Ala101Thr), rs775931500, NCI-TCGA Cosmic COSV9965, cosmic curated COSV99659, ExAC rs775931500, REVEL 0.61, CADD 23.80, Uncertain significance, Inborn genetic diseases; 3-methylcrotonyl-CoA carboxylase 1 deficiency
- A101V (p.Ala101Val), rs772547872, ClinGen CA2719112, ClinVar RCV001996852, ExAC rs772547872, REVEL 0.72, CADD 24.80, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- P102L (p.Pro102Leu), cosmic curated COSV55610, gnomAD rs1387070053, REVEL 0.68, CADD 23.10
- S103F (p.Ser103Phe), cosmic curated COSV10504, TOPMed rs1717921865, gnomAD rs1717921865, REVEL 0.82, CADD 22.70
- Q104* (p.Gln104Ter), TOPMed rs1177891822, CADD 37.00, Pathogenic
- Q104K (p.Gln104Lys), TOPMed rs1177891822, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- Q105* (p.Gln105Ter), cosmic curated COSV10961, TOPMed rs1163620394, gnomAD rs1163620394, CADD 37.00, Pathogenic
- Q105H (p.Gln105His), Ensembl rs1717920438, REVEL 0.66, CADD 24.00, Uncertain significance, not provided
- Q105K (p.Gln105Lys), TOPMed rs1163620394, gnomAD rs1163620394, REVEL 0.60, CADD 22.20, Pathogenic
- Q105R (p.Gln105Arg), rs746430473, ClinGen CA2719111, ClinVar RCV001277565, ClinVar RCV004035450, REVEL 0.70, CADD 26.00, Uncertain significance, Inborn genetic diseases
- S106C (p.Ser106Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Y107C (p.Tyr107Cys), rs144872258, ClinGen CA2719110, ClinVar RCV000818875, ESP rs144872258, REVEL 0.98, CADD 29.00, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- L108V (p.Leu108Val), TOPMed rs1163879867, REVEL 0.89, CADD 25.20
- S109Y (p.Ser109Tyr), ExAC rs748820980
- M110I (p.Met110Ile), ExAC rs777512079, gnomAD rs777512079
- M110T (p.Met110Thr), gnomAD rs1717918837
- M110V (p.Met110Val), TOPMed rs1717919066, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- E111G (p.Glu111Gly), gnomAD rs1717918101, REVEL 0.83, CADD 31.00
- E111K (p.Glu111Lys), ESP rs149905883, TOPMed rs149905883, gnomAD rs149905883, REVEL 0.69, CADD 24.00
- I113V (p.Ile113Val), Ensembl rs1717917373, REVEL 0.53, CADD 23.20
- I114F (p.Ile114Phe), gnomAD rs1294623252, REVEL 0.81, CADD 25.10
- I114V (p.Ile114Val), gnomAD rs1294623252, REVEL 0.38, CADD 22.70
- Q115* (p.Gln115Ter), TOPMed rs920162850, gnomAD rs920162850, CADD 37.00, Pathogenic
- V116A (p.Val116Ala), gnomAD rs1246716621, REVEL 0.73, CADD 22.80
- A117D (p.Ala117Asp), rs754963220, ClinGen CA355319235, ClinVar RCV000810735, ExAC rs754963220, AlphaMissense 0.29, MetaLR 0.96, Uncertain significance, 3-methylcrotonyl-CoA carboxylase 1 deficiency
- A117S (p.Ala117Ser), ExAC rs781171072, gnomAD rs781171072, REVEL 0.90, CADD 25.70
Public MCCC1 analysis runs
- MCCC1 analysis run — MCCC1 (1,096 variants) — completed 2026-08-20