SCN5A (Q14524) variants and mutations
SCN5A (also known as Q14524) is a human protein-coding gene encoding a sodium channel protein type 5 subunit alpha protein. Its rapid inward sodium current drives the upstroke of the cardiac action potential and enables fast electrical conduction through atrial, ventricular, and conduction-system tissue. Pathogenic variants can cause long-QT syndrome type 3, Brugada syndrome, conduction disease, and overlapping arrhythmia phenotypes. This analysis covers 2,486 SCN5A variants and mutations. Of these, 63% have computational variant effect predictions. Disease context includes Brugada syndrome 1, long QT syndrome 3, and progressive familial heart block, type 1A. Example SCN5A variants include M1I, M1L, and M1T.
Variant analysis overview
- Gene: SCN5A
- Protein: Q14524
- UniProt accession: Q14524
- Organism: Homo sapiens
- Variants analyzed: 2486
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 1,877 unspecified-consequence records; 1 stop retained variant; 1 stop lost; 329 missense variants; 196 synonymous variants; 15 stop-gained variants; 5 in-frame insertions; 43 frameshift variants; 17 in-frame deletions; 1 splice-region variants
- Prediction scores: 1,557 variants have prediction scores (63% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Brugada syndrome 1, long QT syndrome 3, progressive familial heart block, type 1A, atrial fibrillation, familial, 10, Brugada syndrome, dilated cardiomyopathy 1E, Familial progressive cardiac conduction defect, cardiac arrhythmia, sick sinus syndrome 1, sudden infant death syndrome, atrial fibrillation, bundle branch block.
Protein structure and variant hotspots
- Protein features: 24 transmembrane segments; 1 domains; 34 post-translational modification sites.
- Structural context: 652 variants have structural context.
- PTM context: 23 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 SCN5A variants
Examples include M1I, M1L, M1T, N3D, N3S, P7L, R8Q, R8W. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs199473550, ClinGen CA017747, ClinVar RCV000058625, MetaLR 0.72, MetaSVM 0.61, not provided, Brugada syndrome
- M1L (p.Met1Leu), rs1553607722, ClinGen CA352159669, ClinVar RCV005400731, MetaLR 0.68, MetaSVM 0.48, Conflicting interpretations, Cardiovascular phenotype; Brugada syndrome 1
- M1T (p.Met1Thr), rs2125936074, ClinGen CA352159666, ClinVar RCV003657619, MetaLR 0.70, MetaSVM 0.55, Uncertain significance, not provided
- N3D (p.Asn3Asp), cosmic curated COSV10810
- N3S (p.Asn3Ser), rs777042523, NCI-TCGA Cosmic COSV6006, cosmic curated COSV60066, ExAC rs777042523, REVEL 0.18, CADD 13.90, Uncertain significance
- P7L (p.Pro7Leu), rs780365654, ClinGen CA352159585, cosmic curated COSV10736, ClinVar RCV002308998, REVEL 0.76, CADD 23.50, Uncertain significance, not provided
- R8Q (p.Arg8Gln), rs564261427, ClinGen CA056648, cosmic curated COSV10964, ClinVar RCV000619935, REVEL 0.45, CADD 22.30, Uncertain significance, Cardiac arrhythmia; Cardiovascular phenotype; not provided
- R8W (p.Arg8Trp), rs1490175548, ClinGen CA352159577, NCI-TCGA Cosmic COSV6006, cosmic curated COSV60066, REVEL 0.66, CADD 25.70, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; not provided
- G9V (p.Gly9Val), rs199473043, ClinGen CA016420, cosmic curated COSV60067, ClinVar RCV000058520, REVEL 0.83, CADD 22.50, Uncertain significance, not provided
- T10I (p.Thr10Ile), rs753443631, ClinGen CA352159524, ClinVar RCV004015757, ClinVar RCV005629000, REVEL 0.56, CADD 22.80, Uncertain significance, not provided; Cardiac arrhythmia
- T10N (p.Thr10Asn), cosmic curated COSV60067, ExAC rs753443631, TOPMed rs753443631, gnomAD rs753443631, REVEL 0.51, CADD 22.60
- S11R (p.Ser11Arg), NCI-TCGA TCGA novel, REVEL 0.39, CADD 19.60, Uncertain significance, not provided
- S12C (p.Ser12Cys), rs2471907097, ClinGen CA352159490, ClinVar RCV003846518, REVEL 0.61, CADD 20.80, Uncertain significance, not provided
- S12G (p.Ser12Gly), rs2471907097, ClinGen CA352159491, ClinVar RCV003278373, Uncertain significance, Cardiovascular phenotype
- R14A (p.Arg14Ala), rs2471907076, ClinGen CA2580069754, ClinVar RCV002323326, ClinVar RCV003658336, Pathogenic
- R14C (p.Arg14Cys), rs763770860, ClinGen CA352159424, cosmic curated COSV60068, ClinVar RCV003541753, REVEL 0.73, CADD 24.80, Uncertain significance, Cardiac arrhythmia; not provided
- R14L (p.Arg14Leu), cosmic curated COSV10002, TOPMed rs1223977399, gnomAD rs1223977399, REVEL 0.61, CADD 22.70, Uncertain significance
- R15S (p.Arg15Ser), NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, Variant assessed as somatic; moderate impact.
- T17I (p.Thr17Ile), rs2471906931, ClinGen CA352159357, ClinVar RCV003658894, Uncertain significance, not provided
- R18L (p.Arg18Leu), cosmic curated COSV60067, REVEL 0.56, CADD 17.30, Uncertain significance, found in a patient with long QT syndrome
- R18Q (p.Arg18Gln), rs41311087, ClinGen CA019208, ClinVar RCV000041626, ClinVar RCV000058779, REVEL 0.66, CADD 17.10, Conflicting interpretations, Cardiac arrhythmia; Cardiovascular phenotype; Brugada syndrome 1
- R18W (p.Arg18Trp), rs199473044, ClinGen CA019099, cosmic curated COSV60066, ClinVar RCV000058764, REVEL 0.84, CADD 24.30, Conflicting interpretations, Cardiac arrhythmia; Cardiovascular phenotype; not specified
- E19K (p.Glu19Lys), cosmic curated COSV60067
- E19Q (p.Glu19Gln), NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, NCI-TCGA Cosmic COSV6006, Variant assessed as somatic; moderate impact.
- E25K (p.Glu25Lys), rs747251132, ClinGen CA019786, cosmic curated COSV60067, ClinVar RCV000171704, REVEL 0.76, CADD 24.30, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; not provided
- R27C (p.Arg27Cys), rs746360906, ClinGen CA056855, NCI-TCGA Cosmic COSV6006, cosmic curated COSV60068, REVEL 0.81, CADD 25.30, Uncertain significance, Cardiac arrhythmia; not provided
- R27H (p.Arg27His), rs199473045, ClinGen CA019812, NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, REVEL 0.83, CADD 23.10, Conflicting interpretations, Cardiac arrhythmia; Cardiovascular phenotype; not provided
- M28I (p.Met28Ile), rs1284557438, ClinGen CA352159062, cosmic curated COSV60067, ClinVar RCV001296119, REVEL 0.18, CADD 6.43, Uncertain significance, Cardiac arrhythmia; not provided
- A29V (p.Ala29Val), rs562675882, ClinGen CA019875, cosmic curated COSV10002, ClinVar RCV000182921, REVEL 0.56, CADD 22.50, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; SCN5A-related disorder
- E30G (p.Glu30Gly), rs199473551, ClinGen CA019935, ClinVar RCV000058861, ClinVar RCV003764739, AlphaMissense 0.11, MetaLR 0.79, Uncertain significance, not specified; not provided
- E30K (p.Glu30Lys), cosmic curated COSV10002, TOPMed rs974585930, Uncertain significance, Cardiac arrhythmia
- K31E (p.Lys31Glu), rs1553607623, ClinGen CA352159018, ClinVar RCV004015482, Uncertain significance, Cardiac arrhythmia
- K31Q (p.Lys31Gln), cosmic curated COSV60067
- Q32* (p.Gln32Ter), rs2062567690, ClinGen CA352158980, ClinVar RCV002374128, ClinVar RCV003546813, AlphaMissense 0.07, MetaLR 0.22, Pathogenic
- A33S (p.Ala33Ser), cosmic curated COSV10810
- A33V (p.Ala33Val), rs1288398293, ClinGen CA352158919, cosmic curated COSV10810, ClinVar RCV001841119, AlphaMissense 0.09, MetaLR 0.73, Uncertain significance, Cardiac arrhythmia
- R34C (p.Arg34Cys), rs6791924, ClinGen CA014158, cosmic curated COSV10645, ClinVar RCV000041594, REVEL 0.54, CADD 23.60, Benign/Likely benign, Cardiac arrhythmia; Cardiovascular phenotype; not specified
- R34H (p.Arg34His), rs199473046, ClinGen CA014189, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, REVEL 0.46, CADD 16.20, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; not provided
- G35S (p.Gly35Ser), rs199473552, ClinGen CA014210, cosmic curated COSV60067, ClinVar RCV000058384, REVEL 0.21, CADD 3.97, Conflicting interpretations, Cardiac arrhythmia; Cardiovascular phenotype; SCN5A-related disorder
- S36* (p.Ser36Ter), cosmic curated COSV10645
- S36L (p.Ser36Leu), rs2062566963, ClinGen CA352158859, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, REVEL 0.12, CADD 15.10, Uncertain significance, not provided
- L39V (p.Leu39Val), rs2471905915, ClinGen CA352158796, ClinVar RCV003841136, REVEL 0.31, CADD 0.18, Uncertain significance, not provided
- E41K (p.Glu41Lys), rs1260906125, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, gnomAD rs1260906125, REVEL 0.41, CADD 13.70, Variant assessed as somatic; moderate impact.
- S42I (p.Ser42Ile), NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, REVEL 0.43, CADD 14.00, Variant assessed as somatic; moderate impact.
- R43* (p.Arg43Ter), rs1553607597, ClinGen CA352158671, NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, CADD 35.00, Pathogenic, in LQT3
- R43Q (p.Arg43Gln), rs199473047, ClinGen CA014665, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, REVEL 0.52, CADD 14.00, Conflicting interpretations, Cardiac arrhythmia; Cardiovascular phenotype; not provided
- G45R (p.Gly45Arg), cosmic curated COSV10736
- P47L (p.Pro47Leu), rs2471905654, ClinGen CA352158584, ClinVar RCV003658451, Uncertain significance, not provided
- E48K (p.Glu48Lys), rs199473048, ClinGen CA014866, cosmic curated COSV10465, ClinVar RCV000058423, REVEL 0.72, CADD 15.00, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; Sick sinus syndrome 1
- E48Q (p.Glu48Gln), cosmic curated COSV10002, Uncertain significance, in LQT3
- P52L (p.Pro52Leu), NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, Uncertain significance, in LQT3
- P52S (p.Pro52Ser), rs199473553, ClinGen CA352158487, ClinVar RCV003567217, UniProt VAR 074697, REVEL 0.82, CADD 22.50, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; Sick sinus syndrome 1
- R53Q (p.Arg53Gln), rs199473049, ClinGen CA015041, NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, REVEL 0.43, CADD 3.44, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; not provided
- R53W (p.Arg53Trp), rs878859550, ClinGen CA72951821, cosmic curated COSV60067, ClinVar RCV001269146, REVEL 0.47, CADD 24.20, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; not specified
- P54L (p.Pro54Leu), rs2471905396, ClinGen CA352158449, ClinVar RCV003658090, Uncertain significance, not provided
- A60T (p.Ala60Thr), rs1407018433, ClinGen CA352158333, ClinVar RCV003136509, AlphaMissense 0.49, MetaLR 0.96, Uncertain significance, not provided
- K63* (p.Lys63Ter), cosmic curated COSV10520, Ensembl rs1553607570
- K63N (p.Lys63Asn), cosmic curated COSV60067, TOPMed rs1460232129, gnomAD rs1460232129, REVEL 0.30, CADD 8.01, Uncertain significance, not provided; Cardiovascular phenotype
- L64P (p.Leu64Pro), NCI-TCGA Cosmic COSV6006, Variant assessed as somatic; moderate impact.
- L64Q (p.Leu64Gln), cosmic curated COSV60067
- P65L (p.Pro65Leu), cosmic curated COSV60068, 1000Genomes rs566155914, ExAC rs566155914, gnomAD rs566155914, REVEL 0.85, CADD 25.00
- D66N (p.Asp66Asn), rs1429845416, NCI-TCGA Cosmic COSV6006, cosmic curated COSV60068, gnomAD rs1429845416, REVEL 0.28, CADD 17.10, Variant assessed as somatic; moderate impact.
- L67F (p.Leu67Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L67R (p.Leu67Arg), cosmic curated COSV60067
- G69A (p.Gly69Ala), rs2471904945, ClinGen CA2580069751, ClinVar RCV003658307, Pathogenic
- G69C (p.Gly69Cys), cosmic curated COSV60067
- N70K (p.Asn70Lys), rs199473050, ClinGen CA015856, ClinVar RCV000058481, ClinVar RCV001699193, REVEL 0.42, CADD 21.10, Uncertain significance, Cardiac arrhythmia; not specified; Sick sinus syndrome 1
- P71A (p.Pro71Ala), rs2471904890, ClinGen CA352158133, ClinVar RCV003658199, Uncertain significance, not provided
- E74* (p.Glu74Ter), cosmic curated COSV10964, gnomAD rs1183868740
- E74D (p.Glu74Asp), rs184966825, ClinGen CA352158055, ClinVar RCV003543216, REVEL 0.20, CADD 7.01, Uncertain significance, not provided
- L75H (p.Leu75His), rs2471904723, ClinGen CA352158044, ClinVar RCV003136505, Uncertain significance, not provided
- G77R (p.Gly77Arg), rs1228779956, ClinGen CA352158017, cosmic curated COSV60067, ClinVar RCV001842688, REVEL 0.78, CADD 24.20, Uncertain significance, Cardiac arrhythmia; Atrial fibrillation, familial, 10; SUDDEN INFANT DEATH SYNDR
- E78D (p.Glu78Asp), cosmic curated COSV10440
- E78K (p.Glu78Lys), NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, Variant assessed as somatic; moderate impact.
- P79S (p.Pro79Ser), rs200923894, ClinGen CA060252, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, REVEL 0.87, CADD 25.40, Uncertain significance, Cardiovascular phenotype
- E81K (p.Glu81Lys), cosmic curated COSV10465, REVEL 0.94, CADD 25.90
- D82G (p.Asp82Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L83M (p.Leu83Met), rs2471904289, ClinGen CA352157897, ClinVar RCV004013134, Uncertain significance, Cardiac arrhythmia
- L83V (p.Leu83Val), rs2471904289, ClinGen CA352157895, ClinVar RCV004012332, REVEL 0.51, CADD 23.30, Uncertain significance, Cardiac arrhythmia
- D84N (p.Asp84Asn), rs199473051, ClinGen CA016221, ClinVar RCV000058505, ClinVar RCV003556149, AlphaMissense 0.91, MetaLR 0.98, Uncertain significance, not provided
- P85L (p.Pro85Leu), cosmic curated COSV60068, REVEL 0.76, CADD 29.10
- S88I (p.Ser88Ile), NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, REVEL 0.65, CADD 21.90, Variant assessed as somatic; moderate impact.
- T89I (p.Thr89Ile), NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, REVEL 0.58, CADD 23.30, Variant assessed as somatic; moderate impact.
- K91M (p.Lys91Met), rs2471903897, ClinGen CA352157704, ClinVar RCV002305023, REVEL 0.91, CADD 28.40, Uncertain significance, Brugada syndrome
- K91N (p.Lys91Asn), rs2125935232, ClinGen CA352157699, cosmic curated COSV60067, ClinVar RCV001842094, REVEL 0.65, CADD 31.00, Uncertain significance, Cardiac arrhythmia
- K91Q (p.Lys91Gln), rs1553607519, ClinGen CA352157717, ClinVar RCV003711673, Uncertain significance, not provided
- T92S (p.Thr92Ser), rs765675330, ClinGen CA352157119, ClinVar RCV003658201, REVEL 0.94, CADD 32.00, Uncertain significance, not provided
- F93S (p.Phe93Ser), rs199473052, ClinGen CA016523, ClinVar RCV000058528, ClinVar RCV006434942, AlphaMissense 0.99, MetaLR 0.97, not provided, Brugada syndrome
- I94M (p.Ile94Met), NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, NCI-TCGA Cosmic COSV6006, Uncertain significance, in BRGDA1
- I94S (p.Ile94Ser), rs199473053, ClinGen CA016537, ClinVar RCV000058530, UniProt VAR 074317, AlphaMissense 0.84, MetaLR 0.93, not provided, Brugada syndrome
- V95I (p.Val95Ile), rs199473054, ClinGen CA016556, cosmic curated COSV60067, ClinVar RCV000058531, REVEL 0.86, CADD 26.00, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; not specified
- L96P (p.Leu96Pro), NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, Variant assessed as somatic; moderate impact.
- N97K (p.Asn97Lys), rs1424823148, ClinGen CA352157090, ClinVar RCV003842379, Uncertain significance, not provided
- K98N (p.Lys98Asn), rs746634595, ClinGen CA352157082, ClinVar RCV003730767, ClinVar RCV006548773, Uncertain significance, Cardiac arrhythmia; not provided
- G99S (p.Gly99Ser), NCI-TCGA Cosmic COSV6006, cosmic curated COSV60068, Uncertain significance, not provided; Cardiac arrhythmia
- T101A (p.Thr101Ala), rs2062506882, ClinGen CA352157064, ClinVar RCV002435860, AlphaMissense 0.53, MetaLR 0.94, Uncertain significance, Cardiovascular phenotype
- F103I (p.Phe103Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R104G (p.Arg104Gly), rs199473055, ClinGen CA016827, ClinVar RCV000058549, ClinVar RCV000434418, AlphaMissense 0.98, MetaLR 0.96, Uncertain significance, not provided
- R104Q (p.Arg104Gln), rs199473554, ClinGen CA016849, ClinVar RCV000058551, ClinVar RCV000182924, REVEL 0.97, CADD 29.60, Conflicting interpretations, Cardiac arrhythmia; Brugada syndrome (shorter-than-normal QT interval); Cardiova
- R104W (p.Arg104Trp), rs199473055, UniProt VAR 074319, AlphaMissense 0.98, MetaLR 0.96, Pathogenic/Likely pathogenic, Cardiovascular phenotype; Brugada syndrome (shorter-than-normal QT interval); no
- A107V (p.Ala107Val), NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, Variant assessed as somatic; moderate impact.
- N109K (p.Asn109Lys), rs199473056, ClinGen CA016995, ClinVar RCV000058560, ClinVar RCV003996535, REVEL 0.36, CADD 14.20, Uncertain significance, Cardiac arrhythmia
- A110T (p.Ala110Thr), rs730880202, ClinGen CA017010, cosmic curated COSV60067, ClinVar RCV000157475, REVEL 0.95, CADD 26.90, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; not specified
- A110V (p.Ala110Val), rs2062505799, ClinGen CA352157006, ClinVar RCV003491443, REVEL 0.96, CADD 27.90, Uncertain significance, not provided
- S115G (p.Ser115Gly), rs199473057, ClinGen CA017168, ClinVar RCV000058572, UniProt VAR 074700, AlphaMissense 0.15, MetaLR 0.91, not provided, Congenital long QT syndrome
- P116F (p.Pro116Phe), cosmic curated COSV60067
- P116L (p.Pro116Leu), cosmic curated COSV10465
- P116S (p.Pro116Ser), cosmic curated COSV60067, Uncertain significance, not provided
- H118P (p.His118Pro), rs2125931643, ClinGen CA352156956, ClinVar RCV003592380, AlphaMissense 0.83, MetaLR 0.92, Uncertain significance, Cardiac arrhythmia
- P119L (p.Pro119Leu), rs758695743, ClinGen CA062052, cosmic curated COSV10736, ClinVar RCV003770622, REVEL 0.68, CADD 23.00, Uncertain significance, not provided; Cardiovascular phenotype; Cardiac arrhythmia
- R121Q (p.Arg121Gln), rs199473058, ClinGen CA017353, NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, REVEL 0.96, CADD 29.90, Pathogenic/Likely pathogenic, Cardiovascular phenotype; not provided; Brugada syndrome 1
- R121W (p.Arg121Trp), rs199473556, ClinGen CA017341, cosmic curated COSV60067, ClinVar RCV000058582, REVEL 0.89, CADD 27.60, Pathogenic/Likely pathogenic, Dilated cardiomyopathy 1E; Brugada syndrome 1; Progressive familial heart block
- R122G (p.Arg122Gly), cosmic curated COSV60067
- A123E (p.Ala123Glu), rs765699394, ClinGen CA352156927, cosmic curated COSV10736, ClinVar RCV003770621, AlphaMissense 0.08, MetaLR 0.68, Uncertain significance, not provided
- A123V (p.Ala123Val), rs765699394, ClinGen CA062209, cosmic curated COSV60067, ClinVar RCV001731897, REVEL 0.24, AlphaMissense 0.08, Uncertain significance, not specified; Cardiovascular phenotype; Brugada syndrome 1
- V125L (p.Val125Leu), rs199473059, ClinGen CA352156920, ClinVar RCV001843238, UniProt VAR 068326, REVEL 0.60, CADD 23.30, Benign/Likely benign, Cardiovascular phenotype; Cardiac arrhythmia; not specified
- K126E (p.Lys126Glu), rs185492581, UniProt VAR 026343, TOPMed rs185492581, gnomAD rs185492581, REVEL 0.93, CADD 25.20, Uncertain significance, Cardiac arrhythmia; not provided
- K126N (p.Lys126Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact., in BRGDA1
- V129A (p.Val129Ala), NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, Variant assessed as somatic; moderate impact.
- L136P (p.Leu136Pro), rs199473557, ClinGen CA017871, ClinVar RCV000058640, ClinVar RCV006434957, AlphaMissense 0.54, MetaLR 0.91, not provided, Brugada syndrome
- L136V (p.Leu136Val), cosmic curated COSV61129, Uncertain significance, in BRGDA1
- M138I (p.Met138Ile), rs199473060, ClinGen CA017919, ClinVar RCV000148866, ClinVar RCV003764737, REVEL 0.87, CADD 23.60, Uncertain significance, not provided
- T140N (p.Thr140Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I141V (p.Ile141Val), rs794728845, ClinGen CA352154763, ClinVar RCV003555049, REVEL 0.94, CADD 22.80, Pathogenic, not provided
- T143A (p.Thr143Ala), rs746026950, ClinGen CA063020, NCI-TCGA Cosmic COSV1003, cosmic curated COSV10034, REVEL 0.79, CADD 24.30, Uncertain significance, Sick sinus syndrome 1; Dilated cardiomyopathy 1E; Progressive familial heart blo
- T143N (p.Thr143Asn), NCI-TCGA TCGA novel, REVEL 0.89, CADD 26.60, Variant assessed as somatic; moderate impact.
- N144T (p.Asn144Thr), rs2471848675, ClinGen CA352154711, ClinVar RCV003860375, ClinVar RCV004006142, REVEL 0.94, CADD 27.00, Uncertain significance, Cardiac arrhythmia; not provided
- V146M (p.Val146Met), rs199473061, ClinGen CA018183, cosmic curated COSV61120, ClinVar RCV000058666, REVEL 0.78, CADD 25.80, Conflicting interpretations, Cardiac arrhythmia; Cardiovascular phenotype; not provided
- M148I (p.Met148Ile), cosmic curated COSV10035
- A149S (p.Ala149Ser), NCI-TCGA TCGA novel, REVEL 0.54, AlphaMissense 0.12, Variant assessed as somatic; moderate impact.
- H151N (p.His151Asn), cosmic curated COSV10465
- H151Y (p.His151Tyr), rs2062340321, ClinGen CA352154617, ClinVar RCV003700625, REVEL 0.46, CADD 24.10, Uncertain significance, not provided
- D152N (p.Asp152Asn), rs778337208, ClinGen CA063420, cosmic curated COSV61117, ClinVar RCV001842104, REVEL 0.30, CADD 21.20, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; not provided
- P154S (p.Pro154Ser), cosmic curated COSV61134
- P155T (p.Pro155Thr), cosmic curated COSV61115, REVEL 0.25, CADD 15.90
- K158N (p.Lys158Asn), rs2471848165, ClinGen CA2697550811, ClinVar RCV003573705, REVEL 0.66, CADD 22.30, Pathogenic
- V160=, rs549015769, NCI-TCGA Cosmic COSV6111, Variant assessed as somatic; low impact.
- E161* (p.Glu161Ter), cosmic curated COSV10885, 1000Genomes rs199473062, ESP rs199473062, ExAC rs199473062, AlphaMissense 0.96, MetaLR 0.97, Pathogenic, in BRGDA1
- E161K (p.Glu161Lys), rs199473062, ClinGen CA018595, ClinVar RCV000058711, UniProt VAR 026344, REVEL 0.96, AlphaMissense 0.96, Pathogenic/Likely pathogenic, Cardiovascular phenotype; Cardiac arrhythmia; not provided
- E161Q (p.Glu161Gln), rs199473062, UniProt VAR 074325, AlphaMissense 0.96, MetaLR 0.97, not provided, Brugada syndrome
- Y162D (p.Tyr162Asp), rs765865175, ClinGen CA352154045, ClinVar RCV004016008, ClinVar RCV005038645, REVEL 0.97, AlphaMissense 0.07, Uncertain significance, SUDDEN INFANT DEATH SYNDROME; Sick sinus syndrome 1; Brugada syndrome 1
- T165I (p.Thr165Ile), rs2471839332, ClinGen CA352153994, ClinVar RCV004007962, Uncertain significance, Cardiac arrhythmia
- A166D (p.Ala166Asp), rs2471839282, ClinGen CA352153980, ClinVar RCV003730086, ClinVar RCV005645769, Uncertain significance, Brugada syndrome 1; not provided
- A166T (p.Ala166Thr), rs201232332, ClinGen CA064027, cosmic curated COSV10736, ClinVar RCV001572069, REVEL 0.80, CADD 27.10, Likely benign, Cardiac arrhythmia; not provided; Cardiovascular phenotype
- I167V (p.Ile167Val), cosmic curated COSV61131, Uncertain significance, not provided
- Y168* (p.Tyr168Ter), rs1435536418, ClinGen CA352153950, ClinVar RCV003492863, Likely pathogenic
- T169A (p.Thr169Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E171G (p.Glu171Gly), rs2062305727, ClinGen CA352153917, cosmic curated COSV61128, ClinVar RCV003656470, AlphaMissense 0.97, MetaLR 0.98, Uncertain significance, not provided
- S172F (p.Ser172Phe), cosmic curated COSV61118
- S172Y (p.Ser172Tyr), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10034, NCI-TCGA Cosmic COSV6111, Variant assessed as somatic; moderate impact.
- L173V (p.Leu173Val), cosmic curated COSV10465, TOPMed rs1257767162, REVEL 0.65, CADD 18.00, Uncertain significance, Cardiovascular phenotype
- V174F (p.Val174Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K175N (p.Lys175Asn), rs199473063, ClinGen CA019045, cosmic curated COSV10590, ClinVar RCV000058757, REVEL 0.80, CADD 25.70, Uncertain significance, not provided
- L177Q (p.Leu177Gln), rs2471838989, ClinGen CA352153853, ClinVar RCV004014283, Uncertain significance, Cardiac arrhythmia
- L177V (p.Leu177Val), rs2471839004, ClinGen CA352153854, ClinVar RCV004014744, REVEL 0.73, CADD 19.50, Uncertain significance, Cardiac arrhythmia
- A178G (p.Ala178Gly), rs199473065, ClinGen CA019140, ClinVar RCV000058772, UniProt VAR 074327, AlphaMissense 0.48, MetaLR 0.97, not provided, Brugada syndrome
- A178T (p.Ala178Thr), NCI-TCGA Cosmic COSV6113, cosmic curated COSV61134, Uncertain significance, in BRGDA1
- R179* (p.Arg179Ter), rs1480085793, ClinGen CA352153836, ClinVar RCV000825605, ClinVar RCV001194085, AlphaMissense 0.11, MetaLR 0.90, Pathogenic
- R179Q (p.Arg179Gln), rs760585484, ClinGen CA064357, NCI-TCGA Cosmic COSV6113, cosmic curated COSV61139, REVEL 0.93, CADD 27.30, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; not provided
- F181L (p.Phe181Leu), rs2471838871, ClinGen CA352153823, ClinVar RCV003668610, Uncertain significance, not provided
- F181V (p.Phe181Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- C182R (p.Cys182Arg), rs199473066, ClinGen CA019232, ClinVar RCV000058781, ClinVar RCV004546427, AlphaMissense 0.96, MetaLR 0.93, Uncertain significance, not provided
- A185T (p.Ala185Thr), rs192113333, ClinGen CA019331, cosmic curated COSV61135, ClinVar RCV000058790, REVEL 0.53, CADD 18.00, Benign/Likely benign, Cardiac arrhythmia; not provided; Brugada syndrome 1
- A185V (p.Ala185Val), rs199473067, ClinGen CA019348, cosmic curated COSV10520, ClinVar RCV000058792, REVEL 0.60, CADD 16.80, Uncertain significance, Cardiac arrhythmia; Sick sinus syndrome 1; Atrial fibrillation, familial, 10
- F186L (p.Phe186Leu), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10034, Variant assessed as somatic; moderate impact.
- T187I (p.Thr187Ile), rs199473558, ClinGen CA064561, ClinVar RCV003139965, ClinVar RCV004689819, AlphaMissense 0.96, MetaLR 0.95, not provided, Brugada syndrome
- R190Q (p.Arg190Gln), rs199473069, ClinGen CA019436, cosmic curated COSV10034, ClinVar RCV000058799, REVEL 0.95, CADD 27.50, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; not specified
- R190W (p.Arg190Trp), rs199473068, ClinGen CA064632, cosmic curated COSV10035, ClinVar RCV001196953, REVEL 0.90, AlphaMissense 0.07, Uncertain significance, Cardiac arrhythmia; Cardiovascular phenotype; not provided
- D191V (p.Asp191Val), cosmic curated COSV10736, NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P192T (p.Pro192Thr), rs2471838491, ClinGen CA352153651, ClinVar RCV002349919, Uncertain significance, Cardiovascular phenotype
- W193* (p.Trp193Ter), cosmic curated COSV10035, Ensembl rs1553605678
- W195* (p.Trp195Ter), rs1553605674, cosmic curated COSV10465, Ensembl rs1553605674, CADD 40.00, Variant assessed as somatic; high impact.
- F198L (p.Phe198Leu), rs2471838206, ClinGen CA352153510, ClinVar RCV002302601, Uncertain significance, not specified
- F198Y (p.Phe198Tyr), cosmic curated COSV61131
- S199G (p.Ser199Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S199R (p.Ser199Arg), cosmic curated COSV10520, Uncertain significance, not provided
- V200A (p.Val200Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V200L (p.Val200Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I201N (p.Ile201Asn), rs2471838060, ClinGen CA352153473, ClinVar RCV003549856, Uncertain significance, not provided
- M203V (p.Met203Val), cosmic curated COSV61138
Public SCN5A analysis runs
- SCN5A analysis run — SCN5A (2,486 variants) — completed 2026-08-19
- SCN5A analysis run — SCN5A (2,486 variants) — completed 2026-08-19
- SCN5A analysis run — SCN5A (2,650 variants) — completed 2026-06-01
- SCN5A analysis run — SCN5A (2,650 variants) — completed 2026-05-30
- SCN5A analysis run — SCN5A (1,846 variants) — completed 2026-05-15