FLNA (Filamin-A) variants and mutations
FLNA (also known as Filamin-A) is a human protein-coding gene encoding a filamin-A protein. It crosslinks actin and connects the cytoskeleton to membrane receptors and signaling proteins during cell migration and tissue morphogenesis. Pathogenic variants cause a broad spectrum including periventricular nodular heterotopia and several skeletal or connective-tissue disorders. This analysis covers 2,953 FLNA variants and mutations. Of these, 69% have computational variant effect predictions. Disease context includes Melnick-Needles syndrome, heterotopia, periventricular, X-linked dominant, and otopalatodigital syndrome type 2. Example FLNA variants include S2C, S2N, and S3G.
Variant analysis overview
- Gene: FLNA
- Protein: Filamin-A
- UniProt accession: P21333
- Organism: Homo sapiens
- Variants analyzed: 2953
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 2,736 unspecified-consequence records; 4 stop lost; 1 stop retained variant; 87 missense variants; 111 synonymous variants; 5 splice-region variants; 1 stop-gained variants; 1 protein altering variant; 2 in-frame insertions; 1 frameshift variants; 3 substitution
- Prediction scores: 2,035 variants have prediction scores (69% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Melnick-Needles syndrome, heterotopia, periventricular, X-linked dominant, otopalatodigital syndrome type 2, otopalatodigital syndrome type 1, frontometaphyseal dysplasia 1, frontometaphyseal dysplasia, cardiac valvular dysplasia, X-linked, terminal osseous dysplasia-pigmentary defects syndrome, Genetic intestinal disease, congenital short bowel syndrome, Terminal osseous dysplasia - pigmentary defects, FG syndrome 2.
Protein structure and variant hotspots
- Protein features: 2 domains; 48 post-translational modification sites.
- Structural context: 174 variants have structural context.
- PTM context: 50 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 FLNA variants
Examples include S2C, S2N, S3G, H5L, H5P, H5Y, S6A, S6F. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- S2C (p.Ser2Cys), rs1391610154, ClinGen CA415255949, ClinVar RCV003404926, ClinVar RCV006561602, REVEL 0.40, CADD 28.10, Uncertain significance, not specified; Oto-palato-digital syndrome, type II; Heterotopia, periventricula
- S2N (p.Ser2Asn), Ensembl rs2148122269
- S3G (p.Ser3Gly), rs1430045418, ClinGen CA415255933, ClinVar RCV002235328, TOPMed rs1430045418, REVEL 0.22, CADD 22.80, Uncertain significance, Frontometaphyseal dysplasia; Oto-palato-digital syndrome, type II; Heterotopia
- H5L (p.His5Leu), rs1557180291, ClinGen CA415255901, ClinVar RCV004534627, AlphaMissense 0.05, MetaLR 0.39, Uncertain significance, FLNA-related disorder
- H5P (p.His5Pro), gnomAD rs1557180291, REVEL 0.45, AlphaMissense 0.05
- H5Y (p.His5Tyr), rs781866647, ClinGen CA10561478, ClinVar RCV000830735, ClinVar RCV001858427, REVEL 0.42, CADD 22.80, Benign/Likely benign, not provided; Frontometaphyseal dysplasia; Oto-palato-digital syndrome, type II
- S6A (p.Ser6Ala), rs1557180289, ClinGen CA415255896, ClinVar RCV003810606, AlphaMissense 0.07, MetaLR 0.22, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Front
- S6F (p.Ser6Phe), rs782780394, ClinGen CA10561477, ClinVar RCV001931371, ClinVar RCV005232724, REVEL 0.26, CADD 23.30, Conflicting interpretations, not provided; Melnick-Needles syndrome; Frontometaphyseal dysplasia
- S6P (p.Ser6Pro), rs1557180289, ClinGen CA415255897, ClinVar RCV000524050, ClinVar RCV001857974, REVEL 0.18, AlphaMissense 0.07, Conflicting interpretations, Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-p
- R7G (p.Arg7Gly), rs941318584, ClinGen CA415255893, cosmic curated COSV10465, ClinVar RCV001300917, REVEL 0.38, CADD 24.90, Conflicting interpretations, Familial thoracic aortic aneurysm and aortic dissection; Frontometaphyseal dyspl
- R7L (p.Arg7Leu), ExAC rs781814342, TOPMed rs781814342, gnomAD rs781814342, REVEL 0.44, CADD 23.20, Likely benign
- R7P (p.Arg7Pro), rs781814342, ClinGen CA10561475, cosmic curated COSV10524, ClinVar RCV001219313, REVEL 0.47, CADD 23.50, Conflicting interpretations, FLNA-related disorder; not provided; Heterotopia, periventricular, X-linked domi
- R7Q (p.Arg7Gln), ExAC rs781814342, TOPMed rs781814342, gnomAD rs781814342, REVEL 0.36, CADD 22.10, Likely benign
- R7W (p.Arg7Trp), rs941318584, ClinGen CA337285541, ClinVar RCV001731831, ClinVar RCV002233043, REVEL 0.37, CADD 32.00, Benign/Likely benign, Melnick-Needles syndrome; Frontometaphyseal dysplasia; Heterotopia, periventricu
- A8V (p.Ala8Val), rs1557180284, ClinGen CA415255886, NCI-TCGA Cosmic COSV1007, cosmic curated COSV10077, AlphaMissense 0.11, MetaLR 0.32, Uncertain significance, Oto-palato-digital syndrome, type II; Heterotopia, periventricular, X-linked dom
- G9C (p.Gly9Cys), rs782292045, ClinGen CA10561473, ClinVar RCV000501455, ClinVar RCV002056848, REVEL 0.31, CADD 21.50, Conflicting interpretations, Heterotopia, periventricular, X-linked dominant; Oto-palato-digital syndrome, ty
- G9D (p.Gly9Asp), Ensembl rs868939799, REVEL 0.23, CADD 18.40
- G9R (p.Gly9Arg), ExAC rs782292045, gnomAD rs782292045, REVEL 0.21, CADD 18.80, Benign
- Q10E (p.Gln10Glu), TOPMed rs1381994072, gnomAD rs1381994072, REVEL 0.19, CADD 21.30
- Q10P (p.Gln10Pro), rs781988041, ClinGen CA415255878, ClinVar RCV003171200, ExAC rs781988041, REVEL 0.41, CADD 22.70, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- Q10R (p.Gln10Arg), rs781988041, ClinGen CA10561472, ClinVar RCV002234288, ClinVar RCV002274101, REVEL 0.23, CADD 19.30, Conflicting interpretations, not provided; Heterotopia, periventricular, X-linked dominant; Oto-palato-digita
- S11I (p.Ser11Ile), ExAC rs782397616, gnomAD rs782397616, REVEL 0.49, CADD 23.50
- S11N (p.Ser11Asn), ExAC rs782397616, gnomAD rs782397616, REVEL 0.18, CADD 21.40
- S11A (p.Ser11Ala), rs868975259, Uncertain significance
- A12E (p.Ala12Glu), rs2522772190, ClinGen CA415255857, ClinVar RCV003799696, REVEL 0.19, CADD 17.40, Uncertain significance, Oto-palato-digital syndrome, type II; Heterotopia, periventricular, X-linked dom
- A12S (p.Ala12Ser), rs868975259, ClinGen CA415255861, ClinVar RCV002232937, gnomAD rs868975259, REVEL 0.17, CADD 14.80, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Front
- A12T (p.Ala12Thr), rs868975259, ClinGen CA415255867, cosmic curated COSV61051, ClinVar RCV002459135, REVEL 0.18, CADD 17.40, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- A13E (p.Ala13Glu), gnomAD rs1557180265, REVEL 0.25, CADD 23.80
- A13V (p.Ala13Val), gnomAD rs1557180265, REVEL 0.25, CADD 22.90
- G14A (p.Gly14Ala), Ensembl rs2067804507, REVEL 0.16, CADD 17.50
- A15E (p.Ala15Glu), rs2522772142, ClinGen CA415255819, ClinVar RCV003023939, ClinVar RCV004763513, REVEL 0.26, CADD 16.50, Uncertain significance, not provided; Melnick-Needles syndrome; Heterotopia, periventricular, X-linked d
- A15S (p.Ala15Ser), rs782034946, ClinGen CA415255822, ClinVar RCV003780656, REVEL 0.24, CADD 18.10, Uncertain significance, Oto-palato-digital syndrome, type II; Heterotopia, periventricular, X-linked dom
- A15T (p.Ala15Thr), rs782034946, NCI-TCGA Cosmic COSV6104, cosmic curated COSV61046, ExAC rs782034946, REVEL 0.23, CADD 21.10, Variant assessed as somatic; moderate impact.
- A16T (p.Ala16Thr), Ensembl rs1557180259
- A16V (p.Ala16Val), rs2522772127, ClinGen CA415255802, ClinVar RCV002881168, REVEL 0.12, CADD 21.80, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Melnick-Needles syndrom
- P17A (p.Pro17Ala), rs1229353720, ClinGen CA415255798, ClinVar RCV003781204, TOPMed rs1229353720, REVEL 0.20, CADD 15.20, Likely benign, Oto-palato-digital syndrome, type II; Heterotopia, periventricular, X-linked dom
- P17L (p.Pro17Leu), rs1057524770, ClinGen CA16608787, ClinVar RCV000423665, gnomAD rs1057524770, REVEL 0.15, CADD 15.80, Uncertain significance, not provided; Familial thoracic aortic aneurysm and aortic dissection
- P17S (p.Pro17Ser), rs1229353720, ClinGen CA415255796, ClinVar RCV002695524, TOPMed rs1229353720, REVEL 0.17, CADD 18.60, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-p
- G18D (p.Gly18Asp), rs2043950991, ClinGen CA415255782, ClinVar RCV003019631, AlphaMissense 0.08, MetaLR 0.30, Uncertain significance, Melnick-Needles syndrome; Heterotopia, periventricular, X-linked dominant; Front
- G18S (p.Gly18Ser), TOPMed rs1291341232, REVEL 0.20, CADD 18.70
- G18V (p.Gly18Val), TOPMed rs2043950991, gnomAD rs2043950991, REVEL 0.14, AlphaMissense 0.08
- G19S (p.Gly19Ser), gnomAD rs1557180253, REVEL 0.11, CADD 8.66, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- G20A (p.Gly20Ala), gnomAD rs1557180246, REVEL 0.20, CADD 7.26
- G20C (p.Gly20Cys), rs1557180247, ClinGen CA415255761, ClinVar RCV002926933, TOPMed rs1557180247, REVEL 0.27, CADD 16.40, Benign, Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia; Melnick-Needl
- G20S (p.Gly20Ser), rs1557180247, ClinGen CA415255764, ClinVar RCV002711911, ClinVar RCV006559609, REVEL 0.15, CADD 10.30, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-p
- G20V (p.Gly20Val), cosmic curated COSV10591, gnomAD rs1557180246, REVEL 0.20, CADD 11.50
- V21A (p.Val21Ala), rs1247203858, ClinGen CA415255743, ClinVar RCV002368787, gnomAD rs1247203858, REVEL 0.15, CADD 5.96, Likely benign, Familial thoracic aortic aneurysm and aortic dissection
- V21F (p.Val21Phe), rs1223954254, ClinGen CA415255748, ClinVar RCV002235303, ClinVar RCV002360982, REVEL 0.14, CADD 1.20, Uncertain significance, Frontometaphyseal dysplasia; Oto-palato-digital syndrome, type II; Heterotopia
- V21G (p.Val21Gly), gnomAD rs1247203858, REVEL 0.18, CADD 11.00, Likely benign
- D22G (p.Asp22Gly), rs782598729, ClinGen CA10561466, cosmic curated COSV61041, ClinVar RCV000513921, REVEL 0.10, CADD 18.70, Conflicting interpretations, Heterotopia, periventricular, X-linked dominant; Oto-palato-digital syndrome, ty
- D22H (p.Asp22His), rs782199446, ClinGen CA10561467, ClinVar RCV002469780, ExAC rs782199446, REVEL 0.18, CADD 17.00, Uncertain significance, not provided
- D22V (p.Asp22Val), ExAC rs782598729, TOPMed rs782598729, gnomAD rs782598729, Benign
- D22Y (p.Asp22Tyr), ExAC rs782199446, TOPMed rs782199446, gnomAD rs782199446, Uncertain significance
- T23A (p.Thr23Ala), rs782244139, ClinGen CA10561465, ClinVar RCV002019411, ClinVar RCV005834176, REVEL 0.12, CADD 9.30, Likely benign, Oto-palato-digital syndrome, type II; Heterotopia, periventricular, X-linked dom
- T23K (p.Thr23Lys), rs1034838081, ClinGen CA415255709, ClinVar RCV003786306, REVEL 0.13, CADD 15.20, Uncertain significance, Oto-palato-digital syndrome, type II; Heterotopia, periventricular, X-linked dom
- T23M (p.Thr23Met), TOPMed rs1034838081, gnomAD rs1034838081, REVEL 0.15, CADD 17.00, Uncertain significance, Melnick-Needles syndrome; Frontometaphyseal dysplasia; Heterotopia, periventricu
- T23P (p.Thr23Pro), ExAC rs782244139, TOPMed rs782244139, gnomAD rs782244139, Likely benign
- R24G (p.Arg24Gly), rs1164930154, ClinGen CA415255706, ClinVar RCV001307455, ClinVar RCV004527819, AlphaMissense 0.25, MetaLR 0.26, Uncertain significance, FLNA-related disorder; Heterotopia, periventricular, X-linked dominant; Oto-pala
- R24L (p.Arg24Leu), rs1350949025, ClinGen CA415255698, ClinVar RCV001944429, ClinVar RCV004042092, REVEL 0.27, CADD 23.50, Conflicting interpretations, not provided; not specified; Familial thoracic aortic aneurysm and aortic dissec
- R24W (p.Arg24Trp), rs1164930154, ClinGen CA415255704, ClinVar RCV001556324, ClinVar RCV002235316, REVEL 0.29, AlphaMissense 0.25, Uncertain significance, Frontometaphyseal dysplasia; Oto-palato-digital syndrome, type II; Heterotopia
- D25E (p.Asp25Glu), rs2522771942, ClinGen CA415255680, ClinVar RCV003807942, REVEL 0.31, CADD 20.40, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Front
- A26P (p.Ala26Pro), rs886038966, ClinGen CA10587975, ClinVar RCV001859453, ClinVar RCV002310891, REVEL 0.47, AlphaMissense 0.10, Conflicting interpretations, Familial thoracic aortic aneurysm and aortic dissection; Melnick-Needles syndrom
- A26S (p.Ala26Ser), NCI-TCGA TCGA novel, REVEL 0.26, CADD 19.10, Variant assessed as somatic; moderate impact.
- A26T (p.Ala26Thr), rs886038966, ClinGen CA415255676, ClinVar RCV001034843, ClinVar RCV002313363, AlphaMissense 0.10, MetaLR 0.40, Uncertain significance, Melnick-Needles syndrome; Frontometaphyseal dysplasia; Heterotopia, periventricu
- A26V (p.Ala26Val), rs782637786, ClinGen CA10561464, ClinVar RCV002233163, ClinVar RCV004535709, REVEL 0.36, CADD 22.90, Conflicting interpretations, FLNA-related disorder; Heterotopia, periventricular, X-linked dominant; Melnick
- E27* (p.Glu27Ter), rs2522771899, ClinGen CA415255663, ClinVar RCV004545866, Likely pathogenic
- E27D (p.Glu27Asp), rs2522771889, ClinGen CA415255652, ClinVar RCV003810605, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Front
- E27K (p.Glu27Lys), rs2522771899, ClinGen CA415255666, ClinVar RCV002419150, REVEL 0.56, CADD 24.20, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- M28I (p.Met28Ile), rs1603363939, ClinGen CA415255639, ClinVar RCV002234234, Ensembl rs1603363939, AlphaMissense 0.88, MetaLR 0.58, Likely pathogenic, Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Front
- M28V (p.Met28Val), rs1557180226, ClinGen CA415255649, ClinVar RCV000577884, Ensembl rs1557180226, AlphaMissense 0.67, MetaLR 0.51, Pathogenic, Heterotopia, periventricular, X-linked dominant
- P29L (p.Pro29Leu), 1000Genomes rs2148122084, REVEL 0.66, CADD 25.00
- E32G (p.Glu32Gly), rs2067803278, ClinGen CA415255605, ClinVar RCV001203099, ClinVar RCV005866854, AlphaMissense 0.94, MetaLR 0.82, Uncertain significance, Frontometaphyseal dysplasia; Heterotopia, periventricular, X-linked dominant; Me
- E32K (p.Glu32Lys), rs1557180220, ClinGen CA415255610, ClinVar RCV003088826, ClinVar RCV004540555, REVEL 0.74, CADD 24.90, Uncertain significance, Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia; Melnick-Needl
- D38N (p.Asp38Asn), cosmic curated COSV10591, gnomAD rs1557180215
- A39G (p.Ala39Gly), rs137853313, ClinGen CA256059, ClinVar RCV000012531, UniProt VAR 022734, AlphaMissense 0.96, MetaLR 0.84, Pathogenic, Heterotopia, periventricular, X-linked dominant
- A39S (p.Ala39Ser), rs2067803076, ClinGen CA415255497, ClinVar RCV001217843, Ensembl rs2067803076, REVEL 0.70, CADD 24.00, Uncertain significance, Frontometaphyseal dysplasia; Heterotopia, periventricular, X-linked dominant; Me
- W41* (p.Trp41Ter), rs2522771786, ClinGen CA415255471, ClinVar RCV003639372, Pathogenic
- W41L (p.Trp41Leu), rs2522771792, ClinGen CA415255473, ClinVar RCV003887275, ClinVar RCV005216141, Uncertain significance, Oto-palato-digital syndrome, type II; Heterotopia, periventricular, X-linked dom
- K42E (p.Lys42Glu), rs2522771783, ClinGen CA415255460, ClinVar RCV004528715, Likely pathogenic, FLNA-related disorder
- K42R (p.Lys42Arg), rs1569551930, ClinGen CA415255455, ClinVar RCV002233290, ClinVar RCV002424658, AlphaMissense 0.64, MetaLR 0.85, Conflicting interpretations, Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Front
- K43N (p.Lys43Asn), rs1569551929, ClinGen CA415255434, ClinVar RCV001044199, Ensembl rs1569551929, AlphaMissense 0.97, MetaLR 0.82, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Oto-palato-digital syndrome, ty
- I44M (p.Ile44Met), rs2067802950, ClinGen CA415255416, ClinVar RCV001091832, Ensembl rs2067802950, AlphaMissense 0.95, MetaLR 0.88, Uncertain significance, not provided
- Q45R (p.Gln45Arg), rs398123613, ClinGen CA221696, ClinVar RCV000079686, ClinVar RCV001527616, AlphaMissense 0.99, MetaLR 0.95, Conflicting interpretations, not provided; Neurodevelopmental delay
- Q46* (p.Gln46Ter), NCI-TCGA Cosmic COSV6104, cosmic curated COSV61045, Variant assessed as somatic; high impact.
- T48P (p.Thr48Pro), rs2522771740, ClinGen CA415255357, ClinVar RCV002832867, Uncertain significance, Oto-palato-digital syndrome, type II; Melnick-Needles syndrome; Frontometaphysea
- T50M (p.Thr50Met), cosmic curated COSV10967, gnomAD rs1557180204, REVEL 0.92, AlphaMissense 0.98, Uncertain significance
- T50R (p.Thr50Arg), rs1557180204, ClinGen CA415255319, ClinVar RCV001509134, gnomAD rs1557180204, AlphaMissense 0.98, MetaLR 0.89, Uncertain significance, not provided
- C53W (p.Cys53Trp), Ensembl rs981888118
- C53Y (p.Cys53Tyr), rs2148122005, ClinGen CA415255267, ClinVar RCV002252414, Ensembl rs2148122005, AlphaMissense 1.00, MetaLR 0.92, Uncertain significance, See cases
- E55K (p.Glu55Lys), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10077, NCI-TCGA Cosmic COSV6103, REVEL 0.88, CADD 25.30, Variant assessed as somatic; moderate impact.
- H56Q (p.His56Gln), rs1569551928, NCI-TCGA TCGA novel, ClinGen CA415255203, ClinVar RCV001548176, AlphaMissense 0.99, MetaLR 0.71, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Front
- H56R (p.His56Arg), rs2148121997, ClinGen CA415255212, ClinVar RCV002028814, ClinVar RCV003389078, AlphaMissense 0.99, MetaLR 0.78, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Oto-palato-digital syndrome, ty
- H56Y (p.His56Tyr), rs2522771675, ClinGen CA415255217, ClinVar RCV003152872, ClinVar RCV006561105, REVEL 0.89, CADD 27.50, Uncertain significance, Oto-palato-digital syndrome, type I; Heterotopia, periventricular, X-linked domi
- K58T (p.Lys58Thr), TOPMed rs2067802562
- C59Y (p.Cys59Tyr), ExAC rs782769930, gnomAD rs782769930, REVEL 0.87, CADD 29.40, Uncertain significance, Melnick-Needles syndrome; Frontometaphyseal dysplasia; Heterotopia, periventricu
- S61N (p.Ser61Asn), rs1557180197, ClinGen CA415255127, cosmic curated COSV10967, ClinVar RCV001299481, REVEL 0.38, CADD 20.60, Uncertain significance, Frontometaphyseal dysplasia; Melnick-Needles syndrome; Oto-palato-digital syndro
- S61T (p.Ser61Thr), rs1557180197, ClinGen CA415255125, ClinVar RCV002467320, REVEL 0.39, CADD 23.90, Uncertain significance, not provided; Familial thoracic aortic aneurysm and aortic dissection
- K62N (p.Lys62Asn), rs2148121969, ClinGen CA415255100, ClinVar RCV001906454, Ensembl rs2148121969, AlphaMissense 0.97, MetaLR 0.80, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Front
- K62R (p.Lys62Arg), rs2148121972, ClinGen CA415255106, ClinVar RCV001886791, Ensembl rs2148121972, REVEL 0.48, CADD 23.70, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Front
- R63H (p.Arg63His), NCI-TCGA TCGA novel, REVEL 0.51, CADD 29.90, Variant assessed as somatic; moderate impact.
- R63L (p.Arg63Leu), rs2067802461, ClinGen CA415255090, ClinVar RCV002408005, ClinVar RCV004763407, REVEL 0.71, CADD 25.10, Uncertain significance, not provided; Familial thoracic aortic aneurysm and aortic dissection
- A65G (p.Ala65Gly), TOPMed rs2067802428
- A65T (p.Ala65Thr), cosmic curated COSV10591, NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A65V (p.Ala65Val), rs2067802428, ClinGen CA415255060, ClinVar RCV002937980, AlphaMissense 0.06, MetaLR 0.54, Uncertain significance, Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia; Melnick-Needl
- N66S (p.Asn66Ser), gnomAD rs1557180196, REVEL 0.55, CADD 24.00
- N66Y (p.Asn66Tyr), rs1569551926, ClinGen CA415255048, ClinVar RCV002233343, Ensembl rs1569551926, AlphaMissense 0.75, MetaLR 0.94, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Front
- Q68H (p.Gln68His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T69M (p.Thr69Met), NCI-TCGA Cosmic COSV6104, cosmic curated COSV61045, Variant assessed as somatic; moderate impact.
- D70Y (p.Asp70Tyr), TOPMed rs2067802334, REVEL 0.98, CADD 29.90, Uncertain significance, not provided
- S72N (p.Ser72Asn), TOPMed rs1557180195, gnomAD rs1557180195, REVEL 0.46, CADD 23.80
- D73H (p.Asp73His), rs1557180192, ClinGen CA415254938, ClinVar RCV000521342, Ensembl rs1557180192, AlphaMissense 1.00, MetaLR 0.97, Uncertain significance, not specified
- A79V (p.Ala79Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A79A (p.Ala79Ala), gnomAD X-154348689-G-T, CADD 4.98
- A79D (p.Ala79Asp), gnomAD X-154348690-G-T, CADD 7.52
- L80V (p.Leu80Val), rs2148121932, ClinGen CA415254838, ClinVar RCV001806363, Ensembl rs2148121932, AlphaMissense 0.69, MetaLR 0.95, Likely pathogenic, Heterotopia, periventricular, X-linked dominant
- E82V (p.Glu82Val), rs28935169, ClinGen CA256055, ClinVar RCV000012520, ClinVar RCV003764561, AlphaMissense 1.00, MetaLR 0.96, Pathogenic, Oto-palato-digital syndrome, type II; Melnick-Needles syndrome; Heterotopia, per
- S85S (p.Ser85Ser), gnomAD X-154348686-G-A, CADD 9.63
- S85R (p.Ser85Arg), gnomAD X-154348686-G-T, CADD 9.03
- S85I (p.Ser85Ile), gnomAD X-154348687-C-A, CADD 9.99
- S85N (p.Ser85Asn), gnomAD X-154348687-C-T, CADD 10.60
- S85G (p.Ser85Gly), gnomAD X-154348688-T-C, CADD 7.65
- Q86R (p.Gln86Arg), ExAC rs782341272, gnomAD rs782341272, REVEL 0.59, CADD 24.70
- H90Y (p.His90Tyr), rs2148121905, ClinGen CA415254661, ClinVar RCV001965630, Ensembl rs2148121905, AlphaMissense 0.05, MetaLR 0.36, Uncertain significance, Oto-palato-digital syndrome, type II; Heterotopia, periventricular, X-linked dom
- R91C (p.Arg91Cys), rs2522771446, ClinGen CA415254642, ClinVar RCV003809522, Uncertain significance, Oto-palato-digital syndrome, type II; Heterotopia, periventricular, X-linked dom
- R91G (p.Arg91Gly), NCI-TCGA Cosmic COSV6104, cosmic curated COSV61044, Variant assessed as somatic; moderate impact.
- R91H (p.Arg91His), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10077, NCI-TCGA Cosmic COSV6105, Variant assessed as somatic; moderate impact.
- H93R (p.His93Arg), rs2148121892, ClinGen CA415254604, ClinVar RCV001751889, Ensembl rs2148121892, AlphaMissense 0.47, MetaLR 0.75, Uncertain significance, not provided
- H93Y (p.His93Tyr), ExAC rs782388981, gnomAD rs782388981, REVEL 0.22, CADD 20.80
- N94D (p.Asn94Asp), rs2522771411, ClinGen CA415254593, ClinVar RCV003040916, Likely pathogenic, Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia; Melnick-Needl
- Q95* (p.Gln95Ter), rs2522771398, ClinGen CA415254570, ClinVar RCV004529295, Likely pathogenic
- R96H (p.Arg96His), rs1046110848, gnomAD X-154348684-C-T, CADD 8.26
- R96C (p.Arg96Cys), gnomAD X-154348685-G-A, CADD 11.00
- R96S (p.Arg96Ser), gnomAD X-154348685-G-T, CADD 10.40
- T98A (p.Thr98Ala), TOPMed rs1569551921, REVEL 0.43, CADD 24.50, Uncertain significance, not provided; Melnick-Needles syndrome; Frontometaphyseal dysplasia
- T98P (p.Thr98Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F99L (p.Phe99Leu), rs2148121887, ClinVar RCV004592208, ClinVar RCV006382261, Uncertain significance, not provided; Melnick-Needles syndrome; Frontometaphyseal dysplasia
- R100C (p.Arg100Cys), NCI-TCGA Cosmic COSV6104, Variant assessed as somatic; moderate impact.
- Q101R (p.Gln101Arg), rs2067801711, ClinGen CA415254483, ClinVar RCV001326927, Ensembl rs2067801711, AlphaMissense 0.97, MetaLR 0.77, Uncertain significance, Frontometaphyseal dysplasia; Melnick-Needles syndrome; Oto-palato-digital syndro
- M102R (p.Met102Arg), rs2067801675, ClinGen CA415254464, ClinVar RCV001339645, Ensembl rs2067801675, AlphaMissense 1.00, MetaLR 0.78, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Front
- M102V (p.Met102Val), UniProt VAR 031305, Pathogenic, in PVNH1
- L104V (p.Leu104Val), rs2522771333, ClinGen CA415254436, ClinVar RCV002994966, ClinVar RCV003146721, Conflicting interpretations, not provided; X-linked FLNA-related disorders; Melnick-Needles syndrome
- V107M (p.Val107Met), rs2148121877, ClinGen CA415254386, cosmic curated COSV10591, ClinVar RCV001817710, AlphaMissense 1.00, MetaLR 0.94, Likely pathogenic, not provided
- S108L (p.Ser108Leu), rs2522771305, ClinGen CA415254362, ClinVar RCV003800876, Uncertain significance, Oto-palato-digital syndrome, type II; Heterotopia, periventricular, X-linked dom
- V109L (p.Val109Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A110V (p.Ala110Val), cosmic curated COSV61052, ExAC rs782275257, gnomAD rs782275257, REVEL 0.85, CADD 24.50
- L111V (p.Leu111Val), rs2522771283, ClinGen CA415254325, ClinVar RCV002454752, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- F113S (p.Phe113Ser), rs1557180178, ClinGen CA415254289, ClinVar RCV002232255, Ensembl rs1557180178, AlphaMissense 1.00, MetaLR 0.93, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Oto-palato-digital syndrome, ty
- R116C (p.Arg116Cys), ExAC rs782298805, gnomAD rs782298805, REVEL 0.66, CADD 32.00
- R116L (p.Arg116Leu), rs2522771236, ClinGen CA415254246, ClinVar RCV003803246, REVEL 0.46, CADD 24.50, Uncertain significance, Oto-palato-digital syndrome, type II; Heterotopia, periventricular, X-linked dom
- S118N (p.Ser118Asn), rs1406549914, ClinGen CA415254216, ClinVar RCV001930557, TOPMed rs1406549914, REVEL 0.30, CADD 19.60, Uncertain significance, Melnick-Needles syndrome; Frontometaphyseal dysplasia; Heterotopia, periventricu
- K120E (p.Lys120Glu), rs2522771207, ClinGen CA415254184, ClinVar RCV004536763, Uncertain significance, FLNA-related disorder
- L121P (p.Leu121Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- D125N (p.Asp125Asn), rs2148121838, ClinGen CA415254085, cosmic curated COSV61054, ClinVar RCV001391265, AlphaMissense 0.99, MetaLR 0.76, Likely pathogenic, Periventricular nodular heterotopia
- A128S (p.Ala128Ser), Ensembl rs1603363301
- A128T (p.Ala128Thr), rs1603363301, ClinGen CA415251144, ClinVar RCV003336019, AlphaMissense 0.89, MetaLR 0.82, Uncertain significance, Cardiac valvular dysplasia, X-linked
- A128V (p.Ala128Val), rs137853315, ClinGen CA256061, ClinVar RCV000012533, ClinVar RCV005887458, AlphaMissense 1.00, MetaLR 0.81, Pathogenic, Heterotopia, periventricular, X-linked dominant
- I129M (p.Ile129Met), rs376726361, ClinGen CA415251096, ClinVar RCV003050680, Uncertain significance, Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia; Melnick-Needl
- V130M (p.Val130Met), rs782151307, ClinGen CA10561413, cosmic curated COSV10524, ClinVar RCV002685459, REVEL 0.92, CADD 26.10, Conflicting interpretations, not provided; Heterotopia, periventricular, X-linked dominant; Melnick-Needles s
- D131E (p.Asp131Glu), rs782315270, ClinGen CA415251043, ClinVar RCV003324417, NCI-TCGA TCGA novel, Uncertain significance, not specified
- G132R (p.Gly132Arg), rs1085307783, ClinGen CA415251018, ClinVar RCV000489668, ClinVar RCV006556079, AlphaMissense 1.00, MetaLR 0.95, Conflicting interpretations, Heterotopia, periventricular, X-linked dominant; Oto-palato-digital syndrome, ty
- N133K (p.Asn133Lys), gnomAD rs1557179686, REVEL 0.59, CADD 23.40
- I137N (p.Ile137Asn), rs1569551877, ClinGen CA415250863, ClinVar RCV002233309, Ensembl rs1569551877, AlphaMissense 1.00, MetaLR 0.95, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Front
- G139R (p.Gly139Arg), rs1557179684, ClinGen CA415250836, ClinVar RCV002313361, Ensembl rs1557179684, AlphaMissense 1.00, MetaLR 0.95, Likely pathogenic, Familial thoracic aortic aneurysm and aortic dissection
- L140F (p.Leu140Phe), rs2148119483, ClinGen CA415250818, ClinVar RCV001808991, ClinVar RCV002542437, AlphaMissense 0.96, MetaLR 0.97, Conflicting interpretations, Heterotopia, periventricular, X-linked dominant; Oto-palato-digital syndrome, ty
- W142L (p.Trp142Leu), rs1057524784, ClinGen CA16608824, ClinVar RCV000427481, Ensembl rs1057524784, AlphaMissense 1.00, MetaLR 0.97, Uncertain significance, not provided
- T143I (p.Thr143Ile), rs1557179679, ClinGen CA415250744, ClinVar RCV000521507, ClinVar RCV003989552, AlphaMissense 1.00, MetaLR 0.91, Uncertain significance, not provided; Heterotopia, periventricular, X-linked dominant
- L144M (p.Leu144Met), NCI-TCGA Cosmic COSV6105, cosmic curated COSV61051, Variant assessed as somatic; moderate impact.
- S149F (p.Ser149Phe), UniProt VAR 031307, Pathogenic, in PVNH1
- S149P (p.Ser149Pro), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10077, Variant assessed as somatic; moderate impact., in PVNH1
- S151C (p.Ser151Cys), Ensembl rs2148119463
- S151F (p.Ser151Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- M152L (p.Met152Leu), Ensembl rs2148119455, REVEL 0.60, CADD 23.80
- M152T (p.Met152Thr), TOPMed rs2067775997, Uncertain significance, FLNA-related disorder
- M154I (p.Met154Ile), rs863223640, gnomAD rs863223640, ClinGen CA324452, ClinVar RCV000199904, REVEL 0.36, CADD 21.90, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Front
- M154R (p.Met154Arg), rs782240483, ClinGen CA415250439, ClinVar RCV003801396, AlphaMissense 0.32, MetaLR 0.74, Uncertain significance, Oto-palato-digital syndrome, type II; Heterotopia, periventricular, X-linked dom
- M154T (p.Met154Thr), rs782240483, ClinGen CA10561407, ClinVar RCV000499997, ClinVar RCV001196653, REVEL 0.74, AlphaMissense 0.32, Conflicting interpretations, Frontometaphyseal dysplasia; Melnick-Needles syndrome; Oto-palato-digital syndro
- W155G (p.Trp155Gly), rs2148119440, ClinGen CA415250400, ClinVar RCV002033374, Ensembl rs2148119440, AlphaMissense 0.92, MetaLR 0.83, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Oto-palato-digital syndrome, ty
- W155S (p.Trp155Ser), rs1557179668, ClinGen CA415250398, ClinVar RCV002232262, Ensembl rs1557179668, REVEL 0.75, CADD 25.00, Uncertain significance, Heterotopia, periventricular, X-linked dominant; Oto-palato-digital syndrome, ty
- D156E (p.Asp156Glu), ExAC rs782657089, gnomAD rs782657089, REVEL 0.38, CADD 0.79, Likely benign
- E157D (p.Glu157Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
Public FLNA analysis runs
- FLNA analysis run — FLNA (2,953 variants) — completed 2026-08-18