SCN4A (Nav1.4) variants and mutations
SCN4A (also known as Nav1.4) is a human protein-coding gene encoding a sodium channel protein type 4 subunit alpha protein. Its rapid sodium current initiates and propagates skeletal-muscle action potentials. Gain- and loss-of-function variants cause disorders of muscle excitability including sodium-channel myotonia, paramyotonia congenita, periodic paralysis, and some congenital myopathies. This analysis covers 3,238 SCN4A variants and mutations. Of these, 73% have computational variant effect predictions. Disease context includes paramyotonia congenita of Von Eulenburg, hyperkalemic periodic paralysis, and potassium-aggravated myotonia. Example SCN4A variants include M1?, A2P, and A2T.
Variant analysis overview
- Gene: SCN4A
- Protein: Nav1.4
- UniProt accession: P35499
- Organism: Homo sapiens
- Variants analyzed: 3238
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 2,783 unspecified-consequence records; 1 stop lost; 223 synonymous variants; 19 frameshift variants; 193 missense variants; 13 in-frame deletions; 2 in-frame insertions; 1 stop-gained variants; 1 splice-region variants; 2 substitution
- Prediction scores: 2,365 variants have prediction scores (73% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: paramyotonia congenita of Von Eulenburg, hyperkalemic periodic paralysis, potassium-aggravated myotonia, hypokalemic periodic paralysis, type 2, congenital myopathy 22B, severe fetal, Congenital myasthenic syndromes, hypokalemic periodic paralysis, congenital myasthenic syndrome 16, Seizure, Pain, congenital myopathy 22A, classic, Postsynaptic congenital myasthenic syndromes.
Protein structure and variant hotspots
- Protein features: 24 transmembrane segments; 1 domains; 11 post-translational modification sites.
- Structural context: 775 variants have structural context.
- PTM context: 15 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, MaveDB, LitVar.
Notable SCN4A variants
Examples include M1?, A2P, A2T, A2V, R3*, R3T, P4S, P4T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA Cosmic COSV7112, Variant assessed as somatic; high impact.
- A2P (p.Ala2Pro), NCI-TCGA Cosmic COSV7112, Variant assessed as somatic; moderate impact.
- A2T (p.Ala2Thr), gnomAD rs1909660941, REVEL 0.45, CADD 24.90
- A2V (p.Ala2Val), rs573062322, ClinGen CA8710310, ClinVar RCV002589791, ClinVar RCV002589792, REVEL 0.47, CADD 27.60, Uncertain significance, Inborn genetic diseases; Hyperkalemic periodic paralysis
- R3* (p.Arg3Ter), Ensembl rs1555605116
- R3T (p.Arg3Thr), rs764134362, ClinGen CA8710309, ClinVar RCV000654666, ClinVar RCV000680093, REVEL 0.20, CADD 6.28, Uncertain significance, Potassium-aggravated myotonia; Congenital myopathy 22A, classic; Congenital myop
- P4S (p.Pro4Ser), TOPMed rs1422062004, gnomAD rs1422062004, REVEL 0.22, CADD 0.04
- P4T (p.Pro4Thr), TOPMed rs1422062004, gnomAD rs1422062004
- S5F (p.Ser5Phe), rs1172123779, gnomAD rs1172123779, REVEL 0.38, CADD 24.20, Variant assessed as somatic; moderate impact.
- L6P (p.Leu6Pro), rs2509325890, ClinGen CA400640627, ClinVar RCV003616365, Uncertain significance, Hyperkalemic periodic paralysis
- C7* (p.Cys7Ter), gnomAD rs1379628025
- C7G (p.Cys7Gly), ExAC rs755865631, gnomAD rs755865631, REVEL 0.25, CADD 4.82
- T8I (p.Thr8Ile), TOPMed rs1909660210, REVEL 0.16, CADD 7.27
- L9M (p.Leu9Met), NCI-TCGA Cosmic COSV7112, Variant assessed as somatic; moderate impact.
- V10L (p.Val10Leu), gnomAD rs1305217778, REVEL 0.21, CADD 15.30
- P11L (p.Pro11Leu), TOPMed rs1047701, Uncertain significance, Potassium-aggravated myotonia; Hypokalemic periodic paralysis, type 2; Hyperkale
- P11S (p.Pro11Ser), NCI-TCGA Cosmic COSV1014, Variant assessed as somatic; moderate impact.
- G13D (p.Gly13Asp), rs1477585952, ClinGen CA400640587, ClinVar RCV003136486, gnomAD rs1477585952, MutPred 0.46, Uncertain significance, not provided
- E15* (p.Glu15Ter), 1000Genomes rs559424913, ExAC rs559424913, gnomAD rs559424913
- E15A (p.Glu15Ala), Ensembl rs1909659506
- E15K (p.Glu15Lys), 1000Genomes rs559424913, ExAC rs559424913, gnomAD rs559424913, REVEL 0.35, CADD 17.80
- E15Q (p.Glu15Gln), 1000Genomes rs559424913, ExAC rs559424913, gnomAD rs559424913, REVEL 0.28, CADD 11.70
- C16* (p.Cys16Ter), ExAC rs765207978, TOPMed rs765207978, gnomAD rs765207978, Likely benign
- C16S (p.Cys16Ser), rs773541890, ClinGen CA8710304, ClinVar RCV000695117, ClinVar RCV002493197, REVEL 0.20, CADD 7.52, Conflicting interpretations, Hyperkalemic periodic paralysis; Potassium-aggravated myotonia; Hypokalemic peri
- L17* (p.Leu17Ter), Ensembl rs1555605111
- L17M (p.Leu17Met), NCI-TCGA Cosmic COSV7112, Variant assessed as somatic; moderate impact.
- R18C (p.Arg18Cys), rs78592515, ClinGen CA8710301, ClinVar RCV001123692, ClinVar RCV001123693, REVEL 0.79, CADD 24.70, Conflicting interpretations, Paramyotonia congenita of Von Eulenburg; Hypokalemic periodic paralysis, type 2
- R18G (p.Arg18Gly), 1000Genomes rs78592515, ESP rs78592515, ExAC rs78592515, TOPMed rs78592515, REVEL 0.77, CADD 24.00, Benign
- R18H (p.Arg18His), rs557359808, ClinGen CA8710299, NCI-TCGA Cosmic COSV7112, REVEL 0.64, CADD 22.60, Uncertain significance, not provided; not specified; Hyperkalemic periodic paralysis
- R18L (p.Arg18Leu), 1000Genomes rs557359808, ExAC rs557359808, TOPMed rs557359808, gnomAD rs557359808, Uncertain significance
- R18S (p.Arg18Ser), rs78592515, ClinGen CA8710300, ClinVar RCV000499480, ClinVar RCV000545405, REVEL 0.67, CADD 23.60, Conflicting interpretations, Hypokalemic periodic paralysis, type 2; Paramyotonia congenita of Von Eulenburg
- P19A (p.Pro19Ala), rs772628295, ClinGen CA8710297, ClinVar RCV000818834, ClinVar RCV004028992, REVEL 0.48, CADD 19.20, Conflicting interpretations, Potassium-aggravated myotonia; Paramyotonia congenita of Von Eulenburg; Hypokale
- P19L (p.Pro19Leu), rs745506979, ClinGen CA8710296, ClinVar RCV002240082, ClinVar RCV006372723, REVEL 0.45, CADD 19.70, Uncertain significance, not specified; Inborn genetic diseases; Hyperkalemic periodic paralysis
- P19S (p.Pro19Ser), rs772628295, ClinGen CA400640555, ClinVar RCV001757932, ClinVar RCV002488519, REVEL 0.53, CADD 21.70, Uncertain significance, Congenital myasthenic syndrome 16; Paramyotonia congenita of Von Eulenburg; Pota
- T21I (p.Thr21Ile), ExAC rs778680199, gnomAD rs778680199, REVEL 0.68, CADD 25.20
- T21P (p.Thr21Pro), Ensembl rs1597988321
- R22G (p.Arg22Gly), rs865873054, ClinGen CA400640539, ClinVar RCV003505585, MutPred 0.51, Uncertain significance, Hyperkalemic periodic paralysis
- R22L (p.Arg22Leu), gnomAD rs1413223155, Uncertain significance
- R22Q (p.Arg22Gln), rs1413223155, ClinGen CA400640538, ClinVar RCV002012255, gnomAD rs1413223155, REVEL 0.35, CADD 17.30, Uncertain significance, Hyperkalemic periodic paralysis
- R22W (p.Arg22Trp), rs865873054, ClinGen CA292972915, ClinVar RCV002047926, ClinVar RCV002498024, REVEL 0.49, CADD 24.90, Uncertain significance, Congenital myasthenic syndrome 16; Paramyotonia congenita of Von Eulenburg; Hypo
- E23K (p.Glu23Lys), rs756692670, ClinGen CA8710294, ClinVar RCV002002760, ExAC rs756692670, REVEL 0.68, CADD 23.70, Uncertain significance, Hyperkalemic periodic paralysis
- L25R (p.Leu25Arg), Ensembl rs1597988301
- A27S (p.Ala27Ser), Ensembl rs2143027823
- I28K (p.Ile28Lys), ExAC rs748862924, TOPMed rs748862924, gnomAD rs748862924
- I28L (p.Ile28Leu), rs886053250, ClinGen CA10646461, ClinVar RCV000259544, ClinVar RCV000293727, REVEL 0.65, CADD 23.80, Uncertain significance, Congenital myasthenic syndrome 16; Paramyotonia congenita of Von Eulenburg; not
- I28T (p.Ile28Thr), ExAC rs748862924, TOPMed rs748862924, gnomAD rs748862924, REVEL 0.79, CADD 24.00
- I28V (p.Ile28Val), TOPMed rs886053250, gnomAD rs886053250, Uncertain significance
- E29G (p.Glu29Gly), rs144347844, ClinGen CA292972909, ClinVar RCV002509925, 1000Genomes rs144347844, Uncertain significance, not provided
- E29K (p.Glu29Lys), TOPMed rs1191299742, gnomAD rs1191299742
- Q30* (p.Gln30Ter), Ensembl rs1555605099
- Q30H (p.Gln30His), rs945475945, ClinGen CA292972907, ClinVar RCV002615551, gnomAD rs945475945, REVEL 0.28, CADD 18.10, Uncertain significance, Hyperkalemic periodic paralysis
- Q30P (p.Gln30Pro), ExAC rs777523942, TOPMed rs777523942, gnomAD rs777523942
- R31L (p.Arg31Leu), rs112142736, ClinGen CA8710289, ClinVar RCV000251549, ClinVar RCV000263314, REVEL 0.56, CADD 23.10, Benign, not specified; not provided; Congenital myasthenic syndrome 16
- R31P (p.Arg31Pro), 1000Genomes rs112142736, ESP rs112142736, ExAC rs112142736, TOPMed rs112142736, REVEL 0.65, CADD 25.10, Benign
- R31Q (p.Arg31Gln), rs112142736, ClinGen CA8710290, ClinVar RCV003086824, ClinVar RCV003138511, REVEL 0.38, CADD 23.10, Uncertain significance, Hyperkalemic periodic paralysis; not provided
- R31W (p.Arg31Trp), rs756059775, ClinGen CA8710291, ClinVar RCV001763055, ClinVar RCV002477931, REVEL 0.68, CADD 28.50, Uncertain significance, Congenital myasthenic syndrome 16; Paramyotonia congenita of Von Eulenburg; Pota
- A32E (p.Ala32Glu), rs765525226, ClinGen CA400640484, ClinVar RCV001066759, ClinVar RCV001128322, REVEL 0.30, CADD 9.78, Uncertain significance, Paramyotonia congenita of Von Eulenburg; Potassium-aggravated myotonia; Hypokale
- A32T (p.Ala32Thr), ExAC rs750577936, gnomAD rs750577936, REVEL 0.18, CADD 14.30
- A32V (p.Ala32Val), rs765525226, ClinGen CA8710286, ClinVar RCV003617047, ExAC rs765525226, REVEL 0.31, CADD 5.32, Uncertain significance, Hyperkalemic periodic paralysis
- V33A (p.Val33Ala), TOPMed rs921149749, gnomAD rs921149749, REVEL 0.18, CADD 0.11, Uncertain significance, Hyperkalemic periodic paralysis
- V33G (p.Val33Gly), TOPMed rs921149749, gnomAD rs921149749
- V33M (p.Val33Met), Ensembl rs374679741, REVEL 0.16, CADD 8.03
- E34* (p.Glu34Ter), Ensembl rs1555605090
- E34D (p.Glu34Asp), NCI-TCGA Cosmic COSV7112, Variant assessed as somatic; moderate impact.
- E35* (p.Glu35Ter), gnomAD rs1220889621
- E35K (p.Glu35Lys), gnomAD rs1220889621
- E36* (p.Glu36Ter), ExAC rs764626013, gnomAD rs764626013
- E36K (p.Glu36Lys), ExAC rs764626013, gnomAD rs764626013, REVEL 0.32, CADD 13.90
- A37G (p.Ala37Gly), Ensembl rs1909655950, REVEL 0.53, CADD 22.40
- A37T (p.Ala37Thr), rs761255954, ClinGen CA8710282, NCI-TCGA Cosmic COSV1014, ClinVar RCV002306247, REVEL 0.53, CADD 18.30, Uncertain significance, Potassium-aggravated myotonia; Congenital myopathy 22A, classic; Hyperkalemic pe
- R38G (p.Arg38Gly), ExAC rs776201356, TOPMed rs776201356, gnomAD rs776201356, Likely benign
- R38L (p.Arg38Leu), ExAC rs772546656, TOPMed rs772546656, gnomAD rs772546656, REVEL 0.28, CADD 15.90, Uncertain significance
- R38Q (p.Arg38Gln), rs772546656, ClinGen CA8710280, ClinVar RCV000483033, ClinVar RCV001323820, REVEL 0.23, CADD 15.70, Uncertain significance, Congenital myasthenic syndrome 16; Hyperkalemic periodic paralysis; Hypokalemic
- R38W (p.Arg38Trp), rs776201356, ClinGen CA8710281, ClinVar RCV002637332, ClinVar RCV003140128, REVEL 0.46, CADD 22.70, Uncertain significance, Hyperkalemic periodic paralysis; not provided
- Q40* (p.Gln40Ter), rs2509325722, ClinGen CA400640440, ClinVar RCV004528763, Likely pathogenic
- Q40R (p.Gln40Arg), Ensembl rs1909655522
- R41G (p.Arg41Gly), NCI-TCGA Cosmic COSV1014, Variant assessed as somatic; moderate impact.
- R41Q (p.Arg41Gln), ExAC rs770640835, TOPMed rs770640835, gnomAD rs770640835, REVEL 0.33, CADD 19.10
- R41W (p.Arg41Trp), rs558855276, ClinGen CA8710278, ClinVar RCV001059609, ClinVar RCV002482043, REVEL 0.46, CADD 24.10, Uncertain significance, not provided; Hyperkalemic periodic paralysis; Paramyotonia congenita of Von Eul
- Q44E (p.Gln44Glu), gnomAD rs1239112997, REVEL 0.30, CADD 14.80
- Q44H (p.Gln44His), TOPMed rs1909655053
- Q44R (p.Gln44Arg), rs2143027631, ClinGen CA400640411, ClinVar RCV002008571, Ensembl rs2143027631, REVEL 0.31, CADD 18.40, Uncertain significance, Hyperkalemic periodic paralysis
- M45V (p.Met45Val), rs2509325711, ClinGen CA400640406, ClinVar RCV004454908, Uncertain significance, Inborn genetic diseases
- E46* (p.Glu46Ter), Ensembl rs1555605080
- E46G (p.Glu46Gly), rs1909654912, ClinGen CA400640394, ClinVar RCV001201623, Ensembl rs1909654912, REVEL 0.28, CADD 20.50, Uncertain significance, Hyperkalemic periodic paralysis
- E46K (p.Glu46Lys), NCI-TCGA Cosmic COSV1014, Variant assessed as somatic; moderate impact.
- I47T (p.Ile47Thr), ExAC rs777343229, gnomAD rs777343229, REVEL 0.30, CADD 16.40
- I47V (p.Ile47Val), TOPMed rs371825957, gnomAD rs371825957, REVEL 0.25, CADD 12.60
- E48* (p.Glu48Ter), ExAC rs769361537, gnomAD rs769361537, CADD 35.00
- E48D (p.Glu48Asp), gnomAD rs1235785007, REVEL 0.19, CADD 8.90
- E49* (p.Glu49Ter), ESP rs368011562, ExAC rs368011562, TOPMed rs368011562, gnomAD rs368011562, Uncertain significance
- E49D (p.Glu49Asp), rs781147290, ClinGen CA8710272, ClinVar RCV001212690, ClinVar RCV005029771, REVEL 0.28, CADD 3.30, Uncertain significance, Hyperkalemic periodic paralysis; Paramyotonia congenita of Von Eulenburg; Potass
- E49G (p.Glu49Gly), gnomAD rs1437988996, REVEL 0.44, CADD 24.30
- E49K (p.Glu49Lys), rs368011562, ClinGen CA8710273, ClinVar RCV001222694, ClinVar RCV002286824, REVEL 0.45, CADD 23.50, Uncertain significance, Inborn genetic diseases; Hyperkalemic periodic paralysis; Hypokalemic periodic p
- E49Q (p.Glu49Gln), ESP rs368011562, ExAC rs368011562, TOPMed rs368011562, gnomAD rs368011562, REVEL 0.48, CADD 23.00, Uncertain significance
- P50A (p.Pro50Ala), rs1267068478, ClinGen CA400640371, ClinVar RCV003204336, REVEL 0.27, CADD 4.26, Uncertain significance, Inborn genetic diseases
- P50S (p.Pro50Ser), TOPMed rs1267068478
- E51* (p.Glu51Ter), ExAC rs751390409, TOPMed rs751390409, gnomAD rs751390409, Uncertain significance
- E51K (p.Glu51Lys), rs751390409, ClinGen CA8710270, ClinVar RCV000654645, ClinVar RCV001169853, REVEL 0.26, CADD 16.30, Uncertain significance, Potassium-aggravated myotonia; Congenital myopathy 22A, classic; Congenital myop
- R52Q (p.Arg52Gln), rs1240011068, ClinGen CA400640358, ClinVar RCV001241953, ClinVar RCV001773547, REVEL 0.15, CADD 13.20, Uncertain significance, not provided; Hyperkalemic periodic paralysis; Hypokalemic periodic paralysis, t
- R52W (p.Arg52Trp), rs201379704, ClinGen CA8710269, ClinVar RCV000607192, ClinVar RCV000680091, REVEL 0.34, CADD 23.00, Conflicting interpretations, not provided; Hyperkalemic periodic paralysis; not specified
- K53* (p.Lys53Ter), Ensembl rs1555605065
- P54T (p.Pro54Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R55* (p.Arg55Ter), ExAC rs754070476, TOPMed rs754070476, gnomAD rs754070476, CADD 37.00, Likely benign
- R55L (p.Arg55Leu), ESP rs376523210, ExAC rs376523210, TOPMed rs376523210, gnomAD rs376523210, Uncertain significance
- R55Q (p.Arg55Gln), rs376523210, ClinGen CA8710266, ClinVar RCV001059084, ClinVar RCV005029640, REVEL 0.24, CADD 19.10, Uncertain significance, Hyperkalemic periodic paralysis; Paramyotonia congenita of Von Eulenburg; Congen
- S56G (p.Ser56Gly), gnomAD rs1349509387, REVEL 0.29, CADD 20.80
- S56I (p.Ser56Ile), TOPMed rs1322711732, gnomAD rs1322711732
- S56T (p.Ser56Thr), TOPMed rs1322711732, gnomAD rs1322711732
- D57E (p.Asp57Glu), rs1415923721, NCI-TCGA Cosmic COSV1014, gnomAD rs1415923721, REVEL 0.48, CADD 22.80, Uncertain significance, Inborn genetic diseases; Hyperkalemic periodic paralysis
- D57G (p.Asp57Gly), TOPMed rs1909652941, REVEL 0.62, CADD 24.30
- D57N (p.Asp57Asn), gnomAD rs1403364987, REVEL 0.56, CADD 23.80
- L58* (p.Leu58Ter), Ensembl rs1555605061
- L58S (p.Leu58Ser), NCI-TCGA TCGA novel, REVEL 0.84, CADD 26.90, Variant assessed as somatic; moderate impact.
- E59* (p.Glu59Ter), TOPMed rs1555605060, gnomAD rs1555605060
- E59D (p.Glu59Asp), 1000Genomes rs199752895, ExAC rs199752895, gnomAD rs199752895, REVEL 0.61, CADD 23.60
- E59K (p.Glu59Lys), TOPMed rs1555605060, gnomAD rs1555605060, REVEL 0.64, CADD 22.40
- G61S (p.Gly61Ser), rs759771825, ClinGen CA8710262, ClinVar RCV001883166, ClinVar RCV005005328, REVEL 0.67, CADD 22.60, Uncertain significance, Hyperkalemic periodic paralysis; Congenital myasthenic syndrome 16; Potassium-ag
- K62* (p.Lys62Ter), Ensembl rs1555605055
- K62N (p.Lys62Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- N63S (p.Asn63Ser), rs941497920, ClinGen CA292972888, ClinVar RCV003136504, ClinVar RCV005021821, REVEL 0.24, CADD 6.40, Uncertain significance, Congenital myopathy 22A, classic; Hyperkalemic periodic paralysis; Potassium-agg
- L64V (p.Leu64Val), rs1480788895, ClinGen CA400640281, ClinVar RCV001873000, ClinVar RCV003247084, REVEL 0.67, CADD 22.80, Uncertain significance, not provided; Hyperkalemic periodic paralysis; Inborn genetic diseases
- P65S (p.Pro65Ser), Ensembl rs1909652066, REVEL 0.87, CADD 25.10
- M66I (p.Met66Ile), gnomAD rs1219877646, NCI-TCGA Cosmic COSV7112, REVEL 0.24, CADD 0.04, Variant assessed as somatic; moderate impact.
- M66V (p.Met66Val), ESP rs374448463, ExAC rs374448463, TOPMed rs374448463, gnomAD rs374448463, REVEL 0.28, CADD 12.50
- I67T (p.Ile67Thr), gnomAD rs1292904922, REVEL 0.70, CADD 23.00
- I67V (p.Ile67Val), rs200834218, ClinGen CA8710260, ClinVar RCV000522802, ClinVar RCV000654647, REVEL 0.49, CADD 21.00, Uncertain significance, Inborn genetic diseases; Hyperkalemic periodic paralysis; Hypokalemic periodic p
- Y68H (p.Tyr68His), ExAC rs762663150, gnomAD rs762663150, REVEL 0.73, CADD 23.10
- G69* (p.Gly69Ter), TOPMed rs886053249, gnomAD rs886053249, Uncertain significance
- G69E (p.Gly69Glu), Ensembl rs982501413
- G69R (p.Gly69Arg), rs886053249, ClinGen CA10650663, ClinVar RCV000268113, ClinVar RCV000307851, REVEL 0.74, CADD 24.10, Uncertain significance, Paramyotonia congenita of Von Eulenburg; not specified; Hyperkalemic periodic pa
- D70E (p.Asp70Glu), ExAC rs769263382, gnomAD rs769263382, REVEL 0.43, CADD 18.40
- D70Y (p.Asp70Tyr), Ensembl rs866082303, REVEL 0.82, CADD 24.50
- P71A (p.Pro71Ala), 1000Genomes rs187055074, ESP rs187055074, ExAC rs187055074, TOPMed rs187055074, Uncertain significance
- P71H (p.Pro71His), ExAC rs781057451, gnomAD rs781057451, REVEL 0.60, CADD 24.10
- P71L (p.Pro71Leu), ExAC rs781057451, gnomAD rs781057451, REVEL 0.42, CADD 19.10
- P71S (p.Pro71Ser), rs187055074, ClinGen CA8710256, ClinVar RCV000713094, ClinVar RCV000808350, REVEL 0.54, CADD 22.60, Conflicting interpretations, not provided; Hyperkalemic periodic paralysis; Potassium-aggravated myotonia
- P71T (p.Pro71Thr), 1000Genomes rs187055074, ESP rs187055074, ExAC rs187055074, TOPMed rs187055074, Uncertain significance, Hyperkalemic periodic paralysis
- P72L (p.Pro72Leu), rs1303471186, ClinGen CA400640230, NCI-TCGA Cosmic COSV7112, ClinVar RCV001318011, REVEL 0.91, CADD 26.20, Uncertain significance, Hyperkalemic periodic paralysis; Potassium-aggravated myotonia; Congenital myast
- P72Q (p.Pro72Gln), TOPMed rs1303471186, gnomAD rs1303471186, REVEL 0.86, CADD 25.60, Uncertain significance, the patient carries a disease-causing CCTG repeat expansion in CNBP
- P72R (p.Pro72Arg), NCI-TCGA Cosmic COSV7112, Uncertain significance, the patient carries a disease-causing CCTG repeat expansion in CNBP
- P72T (p.Pro72Thr), gnomAD rs1351424943, Uncertain significance, the patient carries a disease-causing CCTG repeat expansion in CNBP
- P73L (p.Pro73Leu), rs75086141, ClinGen CA8710253, ClinVar RCV001308968, ClinVar RCV001664819, REVEL 0.28, CADD 21.60, Conflicting interpretations, not specified; Inborn genetic diseases; not provided
- P73S (p.Pro73Ser), gnomAD rs1909650425
- E74* (p.Glu74Ter), TOPMed rs1555605047
- E74Q (p.Glu74Gln), TOPMed rs1555605047
- V75F (p.Val75Phe), rs1909649961, ClinGen CA400640214, ClinVar RCV001992273, Ensembl rs1909649961, Uncertain significance, Hyperkalemic periodic paralysis
- V75G (p.Val75Gly), Ensembl rs1597988088
- I76F (p.Ile76Phe), rs758181972, ClinGen CA8710251, ClinVar RCV004536892, ExAC rs758181972, REVEL 0.57, CADD 23.10, Uncertain significance, SCN4A-related disorder
- I76V (p.Ile76Val), ExAC rs758181972, TOPMed rs758181972, gnomAD rs758181972, REVEL 0.28, CADD 14.60, Uncertain significance
- G77D (p.Gly77Asp), NCI-TCGA Cosmic COSV7112, REVEL 0.62, CADD 23.30, Variant assessed as somatic; moderate impact.
- G77S (p.Gly77Ser), rs369547459, ClinGen CA8710250, ClinVar RCV001047326, ClinVar RCV002552619, REVEL 0.32, CADD 16.30, Uncertain significance, not provided; Hyperkalemic periodic paralysis; Inborn genetic diseases
- I78M (p.Ile78Met), TOPMed rs1382148081, gnomAD rs1382148081, REVEL 0.29, CADD 16.20
- P79A (p.Pro79Ala), 1000Genomes rs376505442, ESP rs376505442, ExAC rs376505442, TOPMed rs376505442, REVEL 0.73, CADD 23.00, Likely benign
- P79L (p.Pro79Leu), gnomAD rs1193392961
- P79S (p.Pro79Ser), rs376505442, ClinGen CA8710248, ClinVar RCV000964702, ClinVar RCV001564401, REVEL 0.80, CADD 25.00, Conflicting interpretations, Paramyotonia congenita of Von Eulenburg; Hypokalemic periodic paralysis, type 2
- P79T (p.Pro79Thr), rs376505442, ClinGen CA8710249, ClinVar RCV000796760, ClinVar RCV000992890, REVEL 0.83, CADD 24.70, Uncertain significance, not provided; Hyperkalemic periodic paralysis
- E81* (p.Glu81Ter), 1000Genomes rs111926172, ESP rs111926172, ExAC rs111926172, TOPMed rs111926172, Benign
- E81D (p.Glu81Asp), TOPMed rs932452404, gnomAD rs932452404, REVEL 0.68, CADD 22.70, Uncertain significance, Inborn genetic diseases
- E81Q (p.Glu81Gln), rs111926172, ClinGen CA8710244, ClinVar RCV000253100, ClinVar RCV000295819, REVEL 0.85, CADD 24.90, Benign, not provided; not specified; Congenital myasthenic syndrome 16
- D82N (p.Asp82Asn), NCI-TCGA Cosmic COSV7112, Variant assessed as somatic; moderate impact.
- L83P (p.Leu83Pro), rs147352060, ClinGen CA8710242, ClinVar RCV000546670, ClinVar RCV001696969, REVEL 0.77, CADD 23.80, Benign/Likely benign, not provided; Hyperkalemic periodic paralysis
- L83V (p.Leu83Val), ExAC rs766753474, gnomAD rs766753474, REVEL 0.33, CADD 21.60
- D84N (p.Asp84Asn), NCI-TCGA Cosmic COSV1014, Variant assessed as somatic; moderate impact.
- Y86C (p.Tyr86Cys), rs372641442, ClinGen CA8710241, ClinVar RCV002756493, ESP rs372641442, REVEL 0.60, CADD 23.00, Uncertain significance, Hyperkalemic periodic paralysis
- Y87* (p.Tyr87Ter), gnomAD rs1454207683, CADD 37.00
- Y87C (p.Tyr87Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Y87H (p.Tyr87His), ExAC rs761254432, gnomAD rs761254432, REVEL 0.88, CADD 26.20
- N89S (p.Asn89Ser), rs1358087685, ClinGen CA400640126, ClinVar RCV003136473, gnomAD rs1358087685, REVEL 0.33, CADD 17.90, Uncertain significance, not provided
- K90N (p.Lys90Asn), Ensembl rs1909647911, REVEL 0.52, CADD 22.40
- K90T (p.Lys90Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T92I (p.Thr92Ile), NCI-TCGA Cosmic COSV7112, Variant assessed as somatic; moderate impact.
- T92N (p.Thr92Asn), gnomAD rs1183711503, REVEL 0.91, CADD 29.50
- F93L (p.Phe93Leu), rs374574341, ClinGen CA400640083, ClinVar RCV001754999, ClinVar RCV006467876, MutPred 0.44, Uncertain significance, not provided; Hyperkalemic periodic paralysis
- I94M (p.Ile94Met), 1000Genomes rs563602704, ExAC rs563602704, TOPMed rs563602704, gnomAD rs563602704, Benign
- I94V (p.Ile94Val), NCI-TCGA Cosmic COSV1014, REVEL 0.38, CADD 20.90, Variant assessed as somatic; moderate impact.
- V95I (p.Val95Ile), rs543813038, NCI-TCGA Cosmic COSV7112, 1000Genomes rs543813038, ExAC rs543813038, REVEL 0.56, CADD 23.10, Uncertain significance, Hyperkalemic periodic paralysis; Congenital myopathy 22B, severe fetal; Paramyot
- V95L (p.Val95Leu), 1000Genomes rs543813038, ExAC rs543813038, gnomAD rs543813038, REVEL 0.71, CADD 23.50, Uncertain significance
- L96R (p.Leu96Arg), TOPMed rs1301917689, gnomAD rs1301917689, REVEL 0.79, CADD 28.40
- N97D (p.Asn97Asp), rs774293481, ClinGen CA8710209, ClinVar RCV003615579, ExAC rs774293481, REVEL 0.56, CADD 23.50, Uncertain significance, Hyperkalemic periodic paralysis
Public SCN4A analysis runs
- SCN4A analysis run — SCN4A (3,238 variants) — completed 2026-08-18