SCN5A (Nav1.5) variants and mutations
SCN5A (also known as Nav1.5) 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 2,422 SCN5A variants and mutations. Of these, 98% 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: Nav1.5
- UniProt accession: Q14524
- Organism: Homo sapiens
- Variants analyzed: 2422
- Variant scope: all variants
- Completed: 2026-10-31
Variant and mutation evidence
- Variant composition: 1,914 unspecified-consequence records; 7 natural variant; 1 stop retained variant; 1 stop lost; 336 missense variants; 196 synonymous variants; 18 stop-gained variants; 5 in-frame insertions; 43 frameshift variants; 17 in-frame deletions; 1 splice-region variants
- Prediction scores: 2,374 variants have prediction scores (98% 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, cardiac arrhythmia, atrial fibrillation, sick sinus syndrome 1, sudden infant death syndrome, bundle branch block, ventricular fibrillation, paroxysmal familial, type 1.
Protein structure and variant hotspots
- Protein features: 24 transmembrane segments; 1 domains; 34 post-translational modification sites.
- Structural context: 624 variants have structural context.
- PTM context: 21 variants overlap post-translational modification sites.
- Experimental data: 54 protein positions have experimental scores. Source: Scores from automatic patch clamping assay of SCN5A variants in HEK293T cells, SCN5A response to veratridine+brevetoxin+ouabain mixture.
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.
Diseases linked to SCN5A
- Long QT syndrome genes and variants
- Dilated cardiomyopathy genes and variants
- Cardiac arrhythmia genes and variants
- Brugada syndrome genes and variants
- Familial atrial fibrillation genes and variants
- Epilepsy genes and variants
- Progressive familial heart block genes and variants
- Sick sinus syndrome genes and variants
- Focal epilepsy genes and variants
- Migraine genes and variants
- Sudden infant death syndrome genes and variants
- Ventricular fibrillation, paroxysmal familial, type 1 genes and variants
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, ESM-1b 0.99, AlphaMissense 0.80, not provided, Brugada syndrome
- M1L (p.Met1Leu), rs1553607722, ClinGen CA352159669, ClinVar RCV005400731, ClinVar RCV006649097, ESM-1b 0.19, AlphaMissense 0.36, Conflicting interpretations, Cardiovascular phenotype; not provided; Brugada syndrome 1
- M1T (p.Met1Thr), rs2125936074, ClinGen CA352159666, ClinVar RCV003657619, ESM-1b 0.22, AlphaMissense 0.67, Uncertain significance, not provided
- N3D (p.Asn3Asp), cosmic curated COSV10810, ESM-1b 0.00, AlphaMissense 0.06
- N3S (p.Asn3Ser), rs777042523, NCI-TCGA Cosmic COSV6006, cosmic curated COSV60066, ExAC rs777042523, REVEL 0.18, ESM-1b 0.00, Uncertain significance
- P7L (p.Pro7Leu), rs780365654, ClinGen CA352159585, cosmic curated COSV10736, ClinVar RCV002308998, REVEL 0.76, ESM-1b 0.00, Uncertain significance, not provided
- R8Q (p.Arg8Gln), rs564261427, ClinGen CA056648, cosmic curated COSV10964, ClinVar RCV000619935, REVEL 0.45, ESM-1b 0.00, Uncertain significance, not provided; Cardiovascular phenotype; Cardiac arrhythmia
- R8W (p.Arg8Trp), rs1490175548, ClinGen CA352159577, NCI-TCGA Cosmic COSV6006, cosmic curated COSV60066, REVEL 0.66, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; not provided
- G9V (p.Gly9Val), rs199473043, ClinGen CA016420, cosmic curated COSV60067, ClinVar RCV000058520, REVEL 0.83, ESM-1b 0.67, Uncertain significance, not provided
- T10I (p.Thr10Ile), rs753443631, ClinGen CA352159524, ClinVar RCV004015757, ClinVar RCV005629000, REVEL 0.56, ESM-1b 0.00, Uncertain significance, not provided; Cardiac arrhythmia
- T10N (p.Thr10Asn), cosmic curated COSV60067, ExAC rs753443631, TOPMed rs753443631, gnomAD rs753443631, REVEL 0.51, ESM-1b 0.00, Uncertain significance
- S12C (p.Ser12Cys), rs2471907097, ClinGen CA352159490, ClinVar RCV003846518, REVEL 0.61, ESM-1b 0.86, Uncertain significance, not provided
- S12G (p.Ser12Gly), rs2471907097, ClinGen CA352159491, ClinVar RCV003278373, ESM-1b 0.00, AlphaMissense 0.09, Uncertain significance, Cardiovascular phenotype
- R14A (p.Arg14Ala), rs2471907076, ClinGen CA2580069754, ClinVar RCV002323326, ClinVar RCV003658336, ESM-1b 0.75, AlphaMissense 0.39, Pathogenic
- R14C (p.Arg14Cys), rs763770860, ClinGen CA352159424, cosmic curated COSV60068, ClinVar RCV003541753, REVEL 0.73, ESM-1b 1.00, Uncertain significance, Cardiac arrhythmia; not provided
- R14L (p.Arg14Leu), cosmic curated COSV10002, TOPMed rs1223977399, gnomAD rs1223977399, REVEL 0.61, ESM-1b 1.00, Uncertain significance
- R15S (p.Arg15Ser), NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, ESM-1b 0.00, AlphaMissense 0.54, Variant assessed as somatic; moderate impact.
- T17I (p.Thr17Ile), rs2471906931, ClinGen CA352159357, ClinVar RCV003658894, ESM-1b 1.00, AlphaMissense 0.83, Uncertain significance, not provided
- R18L (p.Arg18Leu), cosmic curated COSV60067, REVEL 0.56, ESM-1b 0.55, Uncertain significance, found in a patient with long QT syndrome
- R18Q (p.Arg18Gln), rs41311087, ClinGen CA019208, ClinVar RCV000041626, ClinVar RCV000058779, REVEL 0.66, ESM-1b 0.00, Conflicting interpretations, Cardiac arrhythmia; Cardiovascular phenotype; Brugada syndrome 1
- R18W (p.Arg18Trp), rs199473044, ClinGen CA019099, cosmic curated COSV60066, ClinVar RCV000058764, REVEL 0.84, ESM-1b 1.00, Conflicting interpretations, not provided; not specified; Dilated cardiomyopathy 1E
- E19K (p.Glu19Lys), cosmic curated COSV60067, ESM-1b 1.00, AlphaMissense 0.28
- E19Q (p.Glu19Gln), NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, NCI-TCGA Cosmic COSV6006, ESM-1b 1.00, AlphaMissense 0.19, Variant assessed as somatic; moderate impact.
- A22T (p.Ala22Thr), cosmic curated COSV10964, REVEL 0.67, ESM-1b 0.00
- E25K (p.Glu25Lys), rs747251132, ClinGen CA019786, cosmic curated COSV60067, ClinVar RCV000171704, REVEL 0.76, ESM-1b 1.00, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; not provided
- R27C (p.Arg27Cys), rs746360906, ClinGen CA056855, NCI-TCGA Cosmic COSV6006, cosmic curated COSV60068, REVEL 0.81, ESM-1b 1.00, Uncertain significance, Cardiac arrhythmia; not provided
- R27H (p.Arg27His), rs199473045, ClinGen CA019812, NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, REVEL 0.83, ESM-1b 1.00, Conflicting interpretations, not provided; Cardiac arrhythmia; not specified
- M28I (p.Met28Ile), rs1284557438, ClinGen CA352159062, cosmic curated COSV60067, ClinVar RCV001296119, REVEL 0.18, ESM-1b 0.00, Uncertain significance, Cardiac arrhythmia; not provided
- A29V (p.Ala29Val), rs562675882, ClinGen CA019875, cosmic curated COSV10002, ClinVar RCV000182921, REVEL 0.56, ESM-1b 0.76, Uncertain significance, SCN5A-related disorder; Cardiovascular phenotype; Cardiac arrhythmia
- E30G (p.Glu30Gly), rs199473551, ClinGen CA019935, ClinVar RCV000058861, ClinVar RCV003764739, ESM-1b 1.00, AlphaMissense 0.12, Uncertain significance, not specified; not provided
- E30K (p.Glu30Lys), cosmic curated COSV10002, TOPMed rs974585930, ESM-1b 1.00, AlphaMissense 0.12, Uncertain significance, Cardiac arrhythmia
- K31E (p.Lys31Glu), rs1553607623, ClinGen CA352159018, ClinVar RCV004015482, ESM-1b 0.00, AlphaMissense 0.11, Uncertain significance, Cardiac arrhythmia
- K31Q (p.Lys31Gln), cosmic curated COSV60067, ESM-1b 0.00, AlphaMissense 0.10
- Q32* (p.Gln32Ter), rs2062567690, ClinGen CA352158980, ClinVar RCV002374128, ClinVar RCV003546813, MetaLR 0.22, MetaSVM -0.80, Pathogenic
- A33S (p.Ala33Ser), cosmic curated COSV10810, ESM-1b 0.00, AlphaMissense 0.09
- A33V (p.Ala33Val), rs1288398293, ClinGen CA352158919, cosmic curated COSV10810, ClinVar RCV001841119, ESM-1b 0.00, AlphaMissense 0.10, Uncertain significance, Cardiac arrhythmia
- R34C (p.Arg34Cys), rs6791924, ClinGen CA014158, cosmic curated COSV10645, ClinVar RCV000041594, REVEL 0.54, ESM-1b 0.44, 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, ESM-1b 0.00, Uncertain significance, Cardiac arrhythmia; Cardiovascular phenotype; not provided
- G35S (p.Gly35Ser), rs199473552, ClinGen CA014210, cosmic curated COSV60067, ClinVar RCV000058384, REVEL 0.21, ESM-1b 0.00, Conflicting interpretations, not provided; SCN5A-related disorder; Cardiovascular phenotype
- S36* (p.Ser36Ter), cosmic curated COSV10645
- S36L (p.Ser36Leu), rs2062566963, ClinGen CA352158859, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, REVEL 0.12, ESM-1b 0.00, Uncertain significance, not provided
- L39V (p.Leu39Val), rs2471905915, ClinGen CA352158796, ClinVar RCV003841136, REVEL 0.31, ESM-1b 0.00, Uncertain significance, not provided
- E41K (p.Glu41Lys), rs1260906125, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, gnomAD rs1260906125, REVEL 0.41, ESM-1b 0.00, Variant assessed as somatic; moderate impact.
- S42I (p.Ser42Ile), NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, REVEL 0.43, ESM-1b 0.14, Variant assessed as somatic; moderate impact.
- R43* (p.Arg43Ter), rs1553607597, ClinGen CA352158671, NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, CADD 38.00, Pathogenic, in LQT3
- R43Q (p.Arg43Gln), rs199473047, ClinGen CA014665, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, REVEL 0.52, ESM-1b 0.00, Conflicting interpretations, Cardiac arrhythmia; Cardiovascular phenotype; not provided
- E44Q (p.Glu44Gln), cosmic curated COSV11496, ESM-1b 0.00, AlphaMissense 0.09
- G45R (p.Gly45Arg), cosmic curated COSV10736, ESM-1b 0.00, AlphaMissense 0.10
- P47L (p.Pro47Leu), rs2471905654, ClinGen CA352158584, ClinVar RCV003658451, ESM-1b 0.00, AlphaMissense 0.07, Uncertain significance, not provided
- E48K (p.Glu48Lys), rs199473048, ClinGen CA014866, cosmic curated COSV10465, ClinVar RCV000058423, REVEL 0.72, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; Sick sinus syndrome 1
- E48Q (p.Glu48Gln), cosmic curated COSV10002, ESM-1b 0.00, AlphaMissense 0.09, Uncertain significance, in LQT3
- P52L (p.Pro52Leu), NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, ESM-1b 0.00, AlphaMissense 0.07, Uncertain significance, in LQT3
- P52S (p.Pro52Ser), rs199473553, ClinGen CA014968, ClinVar RCV000058428, ClinVar RCV002477194, REVEL 0.82, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; Sick sinus syndrome 1
- P52T (p.Pro52Thr), rs199473553, ClinGen CA352158487, ClinVar RCV003567217, ESM-1b 0.00, AlphaMissense 0.09, Uncertain significance, not provided
- R53Q (p.Arg53Gln), rs199473049, ClinGen CA015041, NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, REVEL 0.43, ESM-1b 0.23, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; not provided
- R53W (p.Arg53Trp), rs878859550, ClinGen CA72951821, cosmic curated COSV60067, ClinVar RCV001269146, REVEL 0.47, ESM-1b 1.00, Uncertain significance, Cardiac arrhythmia; not specified; Cardiovascular phenotype
- P54L (p.Pro54Leu), rs2471905396, ClinGen CA352158449, ClinVar RCV003658090, ESM-1b 1.00, AlphaMissense 0.27, Uncertain significance, not provided
- A60T (p.Ala60Thr), rs1407018433, ClinGen CA352158333, ClinVar RCV003136509, ESM-1b 0.00, AlphaMissense 0.22, 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, ESM-1b 0.00, Uncertain significance, not provided; Cardiovascular phenotype
- L64Q (p.Leu64Gln), cosmic curated COSV60067, ESM-1b 1.00, AlphaMissense 0.89
- P65L (p.Pro65Leu), cosmic curated COSV60068, 1000Genomes rs566155914, ExAC rs566155914, gnomAD rs566155914, REVEL 0.85, ESM-1b 0.99
- D66N (p.Asp66Asn), rs1429845416, NCI-TCGA Cosmic COSV6006, cosmic curated COSV60068, gnomAD rs1429845416, REVEL 0.28, ESM-1b 0.00, Variant assessed as somatic; moderate impact.
- L67R (p.Leu67Arg), cosmic curated COSV60067, ESM-1b 1.00, AlphaMissense 0.32
- G69A (p.Gly69Ala), rs2471904945, ClinGen CA2580069751, ClinVar RCV003658307, ESM-1b 1.00, AlphaMissense 0.30, Pathogenic
- G69C (p.Gly69Cys), cosmic curated COSV60067, ESM-1b 1.00, AlphaMissense 0.36
- N70K (p.Asn70Lys), rs199473050, UniProt VAR 074314, REVEL 0.42, ESM-1b 0.00, Uncertain significance, Cardiac arrhythmia; SCN5A-related disorder; Sick sinus syndrome 1
- P71A (p.Pro71Ala), rs2471904890, ClinGen CA352158133, ClinVar RCV003658199, ESM-1b 0.00, AlphaMissense 0.17, Uncertain significance, not provided
- E74* (p.Glu74Ter), cosmic curated COSV10964, gnomAD rs1183868740
- E74D (p.Glu74Asp), rs184966825, ClinGen CA352158055, ClinVar RCV003543216, REVEL 0.20, ESM-1b 0.48, Uncertain significance, not provided
- L75H (p.Leu75His), rs2471904723, ClinGen CA352158044, ClinVar RCV003136505, ESM-1b 1.00, AlphaMissense 0.51, Uncertain significance, not provided
- G77R (p.Gly77Arg), rs1228779956, ClinGen CA352158017, cosmic curated COSV60067, ClinVar RCV001842688, REVEL 0.78, ESM-1b 1.00, Uncertain significance, Cardiac arrhythmia; Atrial fibrillation, familial, 10; SUDDEN INFANT DEATH SYNDR
- E78D (p.Glu78Asp), cosmic curated COSV10440, ESM-1b 1.00, AlphaMissense 0.48
- E78K (p.Glu78Lys), NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, ESM-1b 1.00, AlphaMissense 0.15, Variant assessed as somatic; moderate impact.
- P79S (p.Pro79Ser), rs200923894, ClinGen CA060252, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, REVEL 0.87, ESM-1b 1.00, Uncertain significance, Cardiovascular phenotype
- E81K (p.Glu81Lys), cosmic curated COSV10465, REVEL 0.94, ESM-1b 1.00
- L83M (p.Leu83Met), rs2471904289, ClinGen CA352157897, ClinVar RCV004013134, ESM-1b 0.77, AlphaMissense 0.13, Uncertain significance, Cardiac arrhythmia
- L83V (p.Leu83Val), rs2471904289, ClinGen CA352157895, ClinVar RCV004012332, REVEL 0.51, ESM-1b 0.00, Uncertain significance, Cardiac arrhythmia
- D84N (p.Asp84Asn), rs199473051, UniProt VAR 074315, ESM-1b 1.00, AlphaMissense 0.89, Uncertain significance, not provided
- D84Y (p.Asp84Tyr), cosmic curated COSV10964, ESM-1b 1.00, AlphaMissense 0.89, Uncertain significance, in BRGDA1
- P85L (p.Pro85Leu), cosmic curated COSV60068, REVEL 0.76, ESM-1b 1.00
- S88I (p.Ser88Ile), NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, REVEL 0.65, ESM-1b 1.00, Variant assessed as somatic; moderate impact.
- T89I (p.Thr89Ile), NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, REVEL 0.58, ESM-1b 0.74, Uncertain significance, not provided
- K91M (p.Lys91Met), rs2471903897, ClinGen CA352157704, ClinVar RCV002305023, REVEL 0.91, ESM-1b 1.00, Uncertain significance, Brugada syndrome
- K91N (p.Lys91Asn), rs2125935232, ClinGen CA352157699, cosmic curated COSV60067, ClinVar RCV001842094, REVEL 0.65, ESM-1b 1.00, Uncertain significance, Cardiac arrhythmia
- K91Q (p.Lys91Gln), rs1553607519, ClinGen CA352157717, ClinVar RCV003711673, ESM-1b 1.00, AlphaMissense 0.26, Uncertain significance, not provided
- T92S (p.Thr92Ser), rs765675330, ClinGen CA352157119, ClinVar RCV003658201, REVEL 0.94, ESM-1b 1.00, Uncertain significance, not provided
- F93S (p.Phe93Ser), rs199473052, UniProt VAR 074316, ESM-1b 1.00, AlphaMissense 0.99, not provided, Brugada syndrome
- I94M (p.Ile94Met), NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, NCI-TCGA Cosmic COSV6006, ESM-1b 1.00, AlphaMissense 0.12, Uncertain significance, in BRGDA1
- I94S (p.Ile94Ser), rs199473053, UniProt VAR 074317, ESM-1b 1.00, AlphaMissense 0.83, Uncertain significance, not provided
- V95I (p.Val95Ile), rs199473054, ClinGen CA016556, cosmic curated COSV60067, ClinVar RCV000058531, REVEL 0.86, ESM-1b 1.00, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; not specified
- L96P (p.Leu96Pro), NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, ESM-1b 1.00, AlphaMissense 0.94, Variant assessed as somatic; moderate impact.
- N97K (p.Asn97Lys), rs1424823148, ClinGen CA352157090, ClinVar RCV003842379, ESM-1b 1.00, AlphaMissense 0.87, Uncertain significance, not provided
- K98N (p.Lys98Asn), rs746634595, ClinGen CA352157082, ClinVar RCV003730767, ClinVar RCV006548773, ESM-1b 1.00, AlphaMissense 0.71, Uncertain significance, Cardiac arrhythmia; not provided
- T101A (p.Thr101Ala), rs2062506882, ClinGen CA352157064, ClinVar RCV002435860, ESM-1b 0.00, AlphaMissense 0.11, Uncertain significance, Cardiovascular phenotype
- R104G (p.Arg104Gly), rs199473055, UniProt VAR 074699, ESM-1b 1.00, AlphaMissense 0.99, Uncertain significance, not provided
- R104Q (p.Arg104Gln), rs199473554, ClinGen CA016849, ClinVar RCV000058551, ClinVar RCV000182924, REVEL 0.97, ESM-1b 1.00, Pathogenic/Likely pathogenic, SCN5A-related disorder; Cardiovascular phenotype; Brugada syndrome (shorter-than
- R104W (p.Arg104Trp), rs199473055, UniProt VAR 074319, ESM-1b 0.87, AlphaMissense 0.88, Pathogenic/Likely pathogenic, not provided; Sick sinus syndrome 1; Brugada syndrome 1
- A107V (p.Ala107Val), NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, ESM-1b 1.00, AlphaMissense 0.77, Variant assessed as somatic; moderate impact.
- N109K (p.Asn109Lys), rs199473056, UniProt VAR 074320, REVEL 0.36, ESM-1b 0.00, Uncertain significance, Cardiac arrhythmia
- A110T (p.Ala110Thr), rs730880202, ClinGen CA017010, cosmic curated COSV60067, ClinVar RCV000157475, REVEL 0.95, ESM-1b 1.00, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; not specified
- A110V (p.Ala110Val), rs2062505799, ClinGen CA352157006, ClinVar RCV003491443, REVEL 0.96, ESM-1b 1.00, Uncertain significance, not provided
- S115G (p.Ser115Gly), rs199473057, UniProt VAR 074700, ESM-1b 0.00, AlphaMissense 0.16, not provided, Congenital long QT syndrome
- P116F (p.Pro116Phe), cosmic curated COSV60067, ESM-1b 1.00, AlphaMissense 0.99
- P116L (p.Pro116Leu), cosmic curated COSV10465, ESM-1b 1.00, AlphaMissense 0.78
- P116S (p.Pro116Ser), cosmic curated COSV60067, ESM-1b 1.00, AlphaMissense 0.71, Uncertain significance, not provided
- H118P (p.His118Pro), rs2125931643, ClinGen CA352156956, ClinVar RCV003592380, ESM-1b 1.00, AlphaMissense 0.51, Uncertain significance, Cardiac arrhythmia
- P119L (p.Pro119Leu), rs758695743, ClinGen CA062052, cosmic curated COSV10736, ClinVar RCV003770622, REVEL 0.68, ESM-1b 1.00, Uncertain significance, not provided; Cardiovascular phenotype; Cardiac arrhythmia
- R121Q (p.Arg121Gln), rs199473058, ClinGen CA017353, NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, REVEL 0.96, ESM-1b 1.00, Pathogenic/Likely pathogenic, not provided; Brugada syndrome 1; SCN5A-related disorder
- R121W (p.Arg121Trp), rs199473556, ClinGen CA017341, cosmic curated COSV60067, ClinVar RCV000058582, REVEL 0.89, ESM-1b 1.00, Pathogenic/Likely pathogenic, Atrial fibrillation, familial, 10; Progressive familial heart block, type 1A; Lo
- R122G (p.Arg122Gly), cosmic curated COSV60067, ESM-1b 1.00, AlphaMissense 0.39
- A123E (p.Ala123Glu), rs765699394, ClinGen CA352156927, cosmic curated COSV10736, ClinVar RCV003770621, ESM-1b 1.00, AlphaMissense 0.45, Uncertain significance, not provided
- A123V (p.Ala123Val), rs765699394, ClinGen CA062209, cosmic curated COSV60067, ClinVar RCV001731897, REVEL 0.24, ESM-1b 0.00, Uncertain significance, not specified; Cardiovascular phenotype; Brugada syndrome 1
- V125L (p.Val125Leu), rs199473059, UniProt VAR 068326, REVEL 0.60, ESM-1b 1.00, Benign/Likely benign, Cardiovascular phenotype; Cardiac arrhythmia; not specified
- K126E (p.Lys126Glu), rs185492581, UniProt VAR 026343, TOPMed rs185492581, gnomAD rs185492581, REVEL 0.93, ESM-1b 1.00, Uncertain significance, Cardiac arrhythmia; not provided
- V129A (p.Val129Ala), NCI-TCGA Cosmic COSV6006, cosmic curated COSV60067, ESM-1b 1.00, AlphaMissense 0.59, Variant assessed as somatic; moderate impact.
- L136P (p.Leu136Pro), rs199473557, ClinGen CA017871, ClinVar RCV000058640, ClinVar RCV006434957, ESM-1b 1.00, AlphaMissense 0.60, not provided, Brugada syndrome
- L136V (p.Leu136Val), cosmic curated COSV61129, ESM-1b 0.00, AlphaMissense 0.11, Uncertain significance, in BRGDA1
- M138I (p.Met138Ile), rs199473060, UniProt VAR 055161, REVEL 0.87, ESM-1b 1.00, Uncertain significance, not provided
- I141V (p.Ile141Val), rs794728845, ClinGen CA352154763, ClinVar RCV003555049, REVEL 0.94, ESM-1b 1.00, Pathogenic/Likely pathogenic, SCN5A-related disorder; not provided
- T143A (p.Thr143Ala), rs746026950, ClinGen CA063020, NCI-TCGA Cosmic COSV1003, cosmic curated COSV10034, REVEL 0.79, ESM-1b 1.00, Uncertain significance, Sick sinus syndrome 1; Dilated cardiomyopathy 1E; Progressive familial heart blo
- N144T (p.Asn144Thr), rs2471848675, ClinGen CA352154711, ClinVar RCV003860375, ClinVar RCV004006142, REVEL 0.94, ESM-1b 1.00, Uncertain significance, Cardiac arrhythmia; not provided
- V146M (p.Val146Met), rs199473061, ClinGen CA018183, cosmic curated COSV61120, ClinVar RCV000058666, REVEL 0.78, ESM-1b 0.30, Conflicting interpretations, Cardiac arrhythmia; Cardiovascular phenotype; not provided
- M148I (p.Met148Ile), cosmic curated COSV10035, ESM-1b 0.89, AlphaMissense 1.00
- H151N (p.His151Asn), cosmic curated COSV10465, ESM-1b 0.00, AlphaMissense 0.09
- H151Y (p.His151Tyr), rs2062340321, ClinGen CA352154617, ClinVar RCV003700625, REVEL 0.46, ESM-1b 0.00, Uncertain significance, not provided
- D152N (p.Asp152Asn), rs778337208, ClinGen CA063420, cosmic curated COSV61117, ClinVar RCV001842104, REVEL 0.30, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; not provided
- P153H (p.Pro153His), cosmic curated COSV11505, REVEL 0.69, ESM-1b 1.00
- P154S (p.Pro154Ser), cosmic curated COSV61134, ESM-1b 0.72, AlphaMissense 0.13
- P155T (p.Pro155Thr), cosmic curated COSV61115, REVEL 0.25, ESM-1b 0.78
- K158N (p.Lys158Asn), rs2471848165, ClinGen CA2697550811, ClinVar RCV003573705, REVEL 0.66, ESM-1b 1.00, Pathogenic
- E161* (p.Glu161Ter), cosmic curated COSV10885, 1000Genomes rs199473062, ESP rs199473062, ExAC rs199473062, CADD 48.00, Pathogenic, in BRGDA1
- E161K (p.Glu161Lys), rs199473062, ClinGen CA018588, cosmic curated COSV61138, ClinVar RCV000058710, REVEL 0.96, ESM-1b 1.00, Pathogenic/Likely pathogenic, Cardiac arrhythmia; SCN5A-related disorder; Cardiovascular phenotype
- E161Q (p.Glu161Gln), rs199473062, UniProt VAR 074325, ESM-1b 1.00, AlphaMissense 0.94, not provided, Brugada syndrome
- Y162D (p.Tyr162Asp), rs765865175, ClinGen CA352154045, ClinVar RCV004016008, ClinVar RCV005038645, REVEL 0.97, ESM-1b 1.00, Uncertain significance, SUDDEN INFANT DEATH SYNDROME; Sick sinus syndrome 1; Brugada syndrome 1
- T165I (p.Thr165Ile), rs2471839332, ClinGen CA352153994, ClinVar RCV004007962, ESM-1b 1.00, AlphaMissense 0.99, Uncertain significance, Cardiac arrhythmia
- A166D (p.Ala166Asp), rs2471839282, ClinGen CA352153980, ClinVar RCV003730086, ClinVar RCV005645769, ESM-1b 1.00, AlphaMissense 0.98, Uncertain significance, Brugada syndrome 1; not provided
- A166T (p.Ala166Thr), rs201232332, ClinGen CA064027, cosmic curated COSV10736, ClinVar RCV001572069, REVEL 0.80, ESM-1b 0.28, Likely benign, Cardiovascular phenotype; Cardiac arrhythmia; not provided
- I167V (p.Ile167Val), cosmic curated COSV61131, ESM-1b 1.00, AlphaMissense 0.15, Uncertain significance, not provided
- Y168* (p.Tyr168Ter), rs1435536418, ClinGen CA352153950, ClinVar RCV003492863, Likely pathogenic
- E171G (p.Glu171Gly), rs2062305727, ClinGen CA352153917, cosmic curated COSV61128, ClinVar RCV003656470, ESM-1b 1.00, AlphaMissense 0.97, Uncertain significance, not provided
- S172F (p.Ser172Phe), cosmic curated COSV61118, ESM-1b 1.00, AlphaMissense 0.79
- S172Y (p.Ser172Tyr), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10034, NCI-TCGA Cosmic COSV6111, ESM-1b 1.00, AlphaMissense 0.84, Variant assessed as somatic; moderate impact.
- L173V (p.Leu173Val), cosmic curated COSV10465, TOPMed rs1257767162, REVEL 0.65, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype
- K175N (p.Lys175Asn), rs199473063, ClinGen CA019045, cosmic curated COSV10590, ClinVar RCV000058757, REVEL 0.80, ESM-1b 1.00, Uncertain significance, not provided
- L177Q (p.Leu177Gln), rs2471838989, ClinGen CA352153853, ClinVar RCV004014283, ESM-1b 1.00, AlphaMissense 0.77, Uncertain significance, Cardiac arrhythmia
- L177V (p.Leu177Val), rs2471839004, ClinGen CA352153854, ClinVar RCV004014744, REVEL 0.73, ESM-1b 0.47, Uncertain significance, Cardiac arrhythmia
- A178G (p.Ala178Gly), rs199473065, UniProt VAR 074327, ESM-1b 1.00, AlphaMissense 0.43, not provided, Brugada syndrome
- A178T (p.Ala178Thr), NCI-TCGA Cosmic COSV6113, cosmic curated COSV61134, ESM-1b 0.57, AlphaMissense 0.81, Uncertain significance, in BRGDA1
- R179Q (p.Arg179Gln), rs760585484, ClinGen CA064357, NCI-TCGA Cosmic COSV6113, cosmic curated COSV61139, REVEL 0.93, ESM-1b 1.00, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; not provided
- F181L (p.Phe181Leu), rs2471838871, ClinGen CA352153823, ClinVar RCV003668610, ESM-1b 1.00, AlphaMissense 0.97, Uncertain significance, not provided
- C182R (p.Cys182Arg), rs199473066, UniProt VAR 074328, ESM-1b 1.00, AlphaMissense 0.79, Uncertain significance, not provided
- C182T (p.Cys182Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A185T (p.Ala185Thr), rs192113333, ClinGen CA019331, cosmic curated COSV61135, ClinVar RCV000058790, REVEL 0.53, ESM-1b 0.00, Benign/Likely benign, not specified; not provided; Brugada syndrome 1
- A185V (p.Ala185Val), rs199473067, ClinGen CA019348, cosmic curated COSV10520, ClinVar RCV000058792, REVEL 0.60, ESM-1b 0.75, Uncertain significance, Cardiac arrhythmia; SCN5A-related disorder; Sick sinus syndrome 1
- F186L (p.Phe186Leu), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10034, ESM-1b 1.00, AlphaMissense 0.99, Variant assessed as somatic; moderate impact.
- T187I (p.Thr187Ile), rs199473558, ClinGen CA019380, ClinVar RCV000058794, ClinVar RCV006434990, ESM-1b 1.00, AlphaMissense 0.93, not provided, Brugada syndrome
- T187C (p.Thr187Cys), NCI-TCGA Cosmic COSV6006, Variant assessed as somatic; moderate impact.
- R190Q (p.Arg190Gln), rs199473069, ClinGen CA019436, cosmic curated COSV10034, ClinVar RCV000058799, REVEL 0.95, ESM-1b 1.00, Uncertain significance, Cardiac arrhythmia; SCN5A-related disorder; Cardiovascular phenotype
- R190W (p.Arg190Trp), rs199473068, ClinGen CA064632, cosmic curated COSV10035, ClinVar RCV001196953, REVEL 0.90, ESM-1b 1.00, Uncertain significance, Cardiac arrhythmia; Cardiovascular phenotype; not provided
- D191V (p.Asp191Val), cosmic curated COSV10736, NCI-TCGA TCGA novel, ESM-1b 1.00, AlphaMissense 0.96, Variant assessed as somatic; moderate impact.
- P192T (p.Pro192Thr), rs2471838491, ClinGen CA352153651, ClinVar RCV002349919, ESM-1b 1.00, AlphaMissense 0.64, Uncertain significance, Cardiovascular phenotype
- W193* (p.Trp193Ter), cosmic curated COSV10035, Ensembl rs1553605678
- W195* (p.Trp195Ter), cosmic curated COSV10465, CADD 43.00
- F198L (p.Phe198Leu), rs2471838206, ClinGen CA352153510, ClinVar RCV002302601, ESM-1b 1.00, AlphaMissense 0.94, Uncertain significance, not specified
- F198Y (p.Phe198Tyr), cosmic curated COSV61131, ESM-1b 1.00, AlphaMissense 0.69
- S199R (p.Ser199Arg), cosmic curated COSV10520, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, not provided
- I201N (p.Ile201Asn), rs2471838060, ClinGen CA352153473, ClinVar RCV003549856, ESM-1b 1.00, AlphaMissense 0.99, Uncertain significance, not provided
- M203V (p.Met203Val), cosmic curated COSV61138, ESM-1b 1.00, AlphaMissense 0.50
- A204T (p.Ala204Thr), rs1378168869, ClinGen CA352153406, cosmic curated COSV61138, ClinVar RCV000781838, REVEL 0.92, ESM-1b 1.00, Uncertain significance, not specified; Brugada syndrome 1
- A204V (p.Ala204Val), rs199473559, ClinGen CA019639, NCI-TCGA Cosmic COSV6111, cosmic curated COSV61118, REVEL 0.97, ESM-1b 1.00, Conflicting interpretations, Cardiovascular phenotype; Cardiac arrhythmia; not provided
- T207A (p.Thr207Ala), rs2062158837, ClinGen CA352151725, NCI-TCGA Cosmic COSV6114, cosmic curated COSV61142, ESM-1b 1.00, AlphaMissense 0.29, Uncertain significance, not provided
- L212P (p.Leu212Pro), rs199473070, UniProt VAR 055162, REVEL 0.97, ESM-1b 1.00, Uncertain significance, not provided
- L212Q (p.Leu212Gln), rs199473070, UniProt VAR 074331, ESM-1b 1.00, AlphaMissense 0.87, Uncertain significance, not provided
- L212V (p.Leu212Val), rs2471802891, ClinGen CA352151664, ClinVar RCV002368968, ClinVar RCV003776242, ESM-1b 1.00, AlphaMissense 0.31, Uncertain significance, not provided; Cardiovascular phenotype
- S216L (p.Ser216Leu), rs41276525, ClinGen CA019682, ClinVar RCV000058831, ClinVar RCV000151805, REVEL 0.96, ESM-1b 1.00, Benign/Likely benign, Congenital long QT syndrome; Cardiac arrhythmia
- A217D (p.Ala217Asp), cosmic curated COSV61136, REVEL 0.99, ESM-1b 1.00
- A217T (p.Ala217Thr), cosmic curated COSV61123, REVEL 0.86, ESM-1b 1.00
- R219C (p.Arg219Cys), rs762012668, ClinGen CA065472, NCI-TCGA Cosmic COSV6111, cosmic curated COSV61116, REVEL 0.92, ESM-1b 1.00, Conflicting interpretations, Brugada syndrome 1; Dilated cardiomyopathy 1E; not provided
- T220I (p.Thr220Ile), rs45620037, ClinGen CA019690, ClinVar RCV000009998, ClinVar RCV000058832, REVEL 0.96, ESM-1b 1.00, Conflicting interpretations, Cardiac arrhythmia; SCN5A-related disorder; Cardiovascular phenotype
Public SCN5A analysis runs
- SCN5A analysis run — SCN5A (2,422 variants) — completed 2026-10-31
- 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