SCN8A (Q9UQD0) variants and mutations
SCN8A (also known as Q9UQD0) is a human protein-coding gene encoding a sodium channel protein type 8 subunit alpha protein. The protein forms Nav1.6, a voltage-gated sodium channel that sets the threshold and propagation of neuronal action potentials. It is widely important for neuronal excitability, and SCN8A variants are associated with developmental and epileptic encephalopathies. This analysis covers 2,504 SCN8A variants and mutations. Of these, 83% have computational variant effect predictions. Disease context includes developmental and epileptic encephalopathy, 13, seizures, benign familial infantile, 5, and Seizure. Example SCN8A variants include A2T, A2V, and A3V.
Variant analysis overview
- Gene: SCN8A
- Protein: Q9UQD0
- UniProt accession: Q9UQD0
- Organism: Homo sapiens
- Variants analyzed: 2504
- Variant scope: all variants
- Completed: 2026-06-05
Variant and mutation evidence
- Variant composition: 2,271 unspecified-consequence records; 86 missense variants; 111 synonymous variants; 7 stop-gained variants; 6 splice-region variants; 5 frameshift variants; 2 in-frame deletions; 15 substitution
- Prediction scores: 2,076 variants have prediction scores (83% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: developmental and epileptic encephalopathy, 13, seizures, benign familial infantile, 5, Seizure, cognitive impairment with or without cerebellar ataxia, epilepsy, partial epilepsy, complex neurodevelopmental disorder, bipolar disorder, Pain, major depressive disorder, migraine disorder, Pruritus.
Protein structure and variant hotspots
- Protein features: 24 transmembrane segments; 1 domains; 3 binding sites; 11 post-translational modification sites.
- Structural context: 543 variants have structural context.
- PTM context: 11 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, PharmGKB, MaveDB, LitVar.
Notable SCN8A variants
Examples include A2T, A2V, A3V, A3T, A3E, A3A, R4Q, R4W. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2T (p.Ala2Thr), rs2138670848, ClinGen CA385227385, ClinVar RCV002016465, Ensembl rs2138670848, ESM-1b 0.00, AlphaMissense 0.63, Uncertain significance, Early-infantile DEE
- A2V (p.Ala2Val), gnomAD 12-51662822-C-T, REVEL 0.79, ESM-1b 0.21
- A3V (p.Ala3Val), rs758891499, ClinGen CA6570983, NCI-TCGA Cosmic COSV6198, cosmic curated COSV61981, REVEL 0.47, ESM-1b 0.00, Uncertain significance, Early-infantile DEE; Inborn genetic diseases
- A3T (p.Ala3Thr), gnomAD 12-51662824-G-A, REVEL 0.53, ESM-1b 0.00
- A3E (p.Ala3Glu), gnomAD 12-51662825-C-A, REVEL 0.48, ESM-1b 0.00
- A3A (p.Ala3Ala), rs778177119, gnomAD 12-51662826-G-A, CADD 10.40
- R4Q (p.Arg4Gln), rs751889285, ClinGen CA6570985, cosmic curated COSV61993, ClinVar RCV000520832, REVEL 0.22, ESM-1b 0.00, Uncertain significance, Early-infantile DEE; not provided
- R4W (p.Arg4Trp), rs1940949996, ClinGen CA385227396, cosmic curated COSV10591, ClinVar RCV001320296, REVEL 0.53, ESM-1b 0.50, Uncertain significance, Early-infantile DEE
- R4R (p.Arg4Arg), gnomAD 12-51662829-G-A, CADD 13.10
- L5L (p.Leu5Leu), rs757637034, gnomAD 12-51662832-G-C, CADD 10.90
- L6H (p.Leu6His), gnomAD 12-51662834-T-A, REVEL 0.89, ESM-1b 0.00
- A7E (p.Ala7Glu), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10063, ESM-1b 0.00, AlphaMissense 0.57, Variant assessed as somatic; moderate impact.
- A7P (p.Ala7Pro), rs896109778, ClinGen CA385227412, NCI-TCGA Cosmic COSV6198, cosmic curated COSV61980, ESM-1b 0.00, AlphaMissense 0.23, Uncertain significance, not provided
- A7S (p.Ala7Ser), TOPMed rs896109778, REVEL 0.47, ESM-1b 0.00, Uncertain significance
- A7T (p.Ala7Thr), gnomAD 12-51662836-G-A, REVEL 0.42, ESM-1b 0.00
- A7V (p.Ala7Val), gnomAD 12-51662837-C-T, REVEL 0.43, ESM-1b 0.00
- P8A (p.Pro8Ala), ExAC rs780814153, gnomAD rs780814153, REVEL 0.80, ESM-1b 0.16
- P9P (p.Pro9Pro), rs1204132838, gnomAD 12-51662844-A-G, CADD 14.60
- G10G (p.Gly10Gly), rs1256810700, gnomAD 12-51662847-C-G, CADD 13.10
- P11L (p.Pro11Leu), rs745556675, ExAC rs745556675, gnomAD rs745556675, REVEL 0.81, ESM-1b 1.00, Variant assessed as somatic; moderate impact.
- P11T (p.Pro11Thr), rs1940950511, ClinGen CA385227433, ClinVar RCV001238746, Ensembl rs1940950511, ESM-1b 1.00, AlphaMissense 0.50, Likely benign, Early-infantile DEE
- P11H (p.Pro11His), gnomAD 12-51662849-C-A, REVEL 0.82, ESM-1b 1.00
- D12E (p.Asp12Glu), rs1185519570, ClinGen CA385227445, ClinVar RCV001374158, TOPMed rs1185519570, ESM-1b 0.00, AlphaMissense 0.16, Uncertain significance, Early-infantile DEE
- D12G (p.Asp12Gly), rs1565878368, ClinGen CA385227442, ClinVar RCV002318061, Ensembl rs1565878368, ESM-1b 0.18, AlphaMissense 0.28, Uncertain significance, Inborn genetic diseases
- D12N (p.Asp12Asn), TOPMed rs1940950636, REVEL 0.36, ESM-1b 0.00
- D12D (p.Asp12Asp), rs1185519570, gnomAD 12-51662853-T-C, AlphaMissense 0.16, MetaLR 0.62
- K15* (p.Lys15Ter), Ensembl rs1555214259
- P16L (p.Pro16Leu), rs1940950901, ClinGen CA385227490, ClinVar RCV001054639, Ensembl rs1940950901, ESM-1b 1.00, AlphaMissense 0.10, Uncertain significance, Early-infantile DEE
- P16A (p.Pro16Ala), gnomAD 12-51662863-C-G, REVEL 0.22, ESM-1b 1.00
- P16P (p.Pro16Pro), gnomAD 12-51662865-T-C, CADD 12.70
- F17L (p.Phe17Leu), rs1592363287, ClinGen CA385227505, ClinVar RCV000795327, Ensembl rs1592363287, ESM-1b 1.00, AlphaMissense 0.97, Uncertain significance, Early-infantile DEE
- P19R (p.Pro19Arg), rs1940951099, ClinGen CA385227526, ClinVar RCV001351855, Ensembl rs1940951099, ESM-1b 0.00, AlphaMissense 0.06, Uncertain significance, Early-infantile DEE; not provided
- P19S (p.Pro19Ser), gnomAD rs1368026224, ESM-1b 0.10, AlphaMissense 0.19
- P19T (p.Pro19Thr), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10063, REVEL 0.40, ESM-1b 0.65, Variant assessed as somatic; moderate impact.
- P19L (p.Pro19Leu), gnomAD 12-51662873-C-T, REVEL 0.34, ESM-1b 0.80
- P19P (p.Pro19Pro), rs1450138204, gnomAD 12-51662874-T-C, CADD 9.25
- E20* (p.Glu20Ter), rs1555214261, NCI-TCGA Cosmic COSV1006, cosmic curated COSV10063, Ensembl rs1555214261, Variant assessed as somatic; high impact.
- E20D (p.Glu20Asp), rs1940951373, ClinGen CA385227540, ClinVar RCV001368961, ClinVar RCV002357255, ESM-1b 0.00, AlphaMissense 0.20, Uncertain significance, Inborn genetic diseases; Early-infantile DEE
- S21* (p.Ser21Ter), gnomAD 12-51662879-C-A, CADD 35.00
- L22L (p.Leu22Leu), gnomAD 12-51662881-C-T, CADD 12.70
- A23S (p.Ala23Ser), rs2540119153, ClinGen CA385227564, ClinVar RCV002369485, ESM-1b 0.64, AlphaMissense 0.13, Uncertain significance, Inborn genetic diseases
- N24D (p.Asn24Asp), rs1170755479, ClinGen CA385227577, ClinVar RCV000796706, TOPMed rs1170755479, REVEL 0.26, ESM-1b 0.00, Uncertain significance, Early-infantile DEE
- N24S (p.Asn24Ser), rs769269501, ClinGen CA6570989, ClinVar RCV000768310, ClinVar RCV002370026, REVEL 0.25, ESM-1b 0.00, Uncertain significance, Early-infantile DEE; Developmental and epileptic encephalopathy, 13; Cognitive i
- I25T (p.Ile25Thr), ExAC rs779565282, gnomAD rs779565282, REVEL 0.80, ESM-1b 1.00
- E26* (p.Glu26Ter), Ensembl rs1555214267
- E26D (p.Glu26Asp), TOPMed rs1940951822, REVEL 0.87, ESM-1b 1.00
- E26K (p.Glu26Lys), Ensembl rs1555214267, REVEL 0.91, ESM-1b 1.00
- R27K (p.Arg27Lys), rs1303731165, ClinGen CA385227624, ClinVar RCV001360025, ClinVar RCV003490221, REVEL 0.24, ESM-1b 0.00, Uncertain significance, not specified; Early-infantile DEE
- R27R (p.Arg27Arg), rs748777974, gnomAD 12-51662898-G-A, CADD 12.90
- R28C (p.Arg28Cys), rs768570935, ClinGen CA6570992, NCI-TCGA Cosmic COSV6198, cosmic curated COSV61980, REVEL 0.87, ESM-1b 1.00, Conflicting interpretations, Early-infantile DEE; Inborn genetic diseases; not provided
- R28H (p.Arg28His), rs531796685, ClinGen CA6570993, cosmic curated COSV10648, ClinVar RCV001918356, REVEL 0.78, ESM-1b 1.00, Uncertain significance, Early-infantile DEE
- R28L (p.Arg28Leu), gnomAD 12-51662900-G-T, REVEL 0.76, ESM-1b 1.00
- I29L (p.Ile29Leu), rs2540119199, ClinGen CA385227642, ClinVar RCV002806476, ClinVar RCV003138361, ESM-1b 0.00, AlphaMissense 0.22, Uncertain significance, not provided; Early-infantile DEE
- A30T (p.Ala30Thr), rs2138671059, ClinGen CA385227654, ClinVar RCV001892406, Ensembl rs2138671059, ESM-1b 0.00, AlphaMissense 0.09, Uncertain significance, Early-infantile DEE
- E31* (p.Glu31Ter), Ensembl rs1555214272
- E31E (p.Glu31Glu), gnomAD 12-51662910-G-A, CADD 9.41
- S32N (p.Ser32Asn), rs375419028, ClinGen CA6570994, ClinVar RCV000802422, ClinVar RCV001091241, REVEL 0.41, ESM-1b 0.00, Conflicting interpretations, Early-infantile DEE; not provided
- S32G (p.Ser32Gly), gnomAD 12-51662911-A-G, REVEL 0.41, ESM-1b 0.00
- S32S (p.Ser32Ser), gnomAD 12-51662913-C-T, CADD 13.30
- K33* (p.Lys33Ter), Ensembl rs1555214273
- K33K (p.Lys33Lys), gnomAD 12-51662916-G-A, CADD 9.39
- L34F (p.Leu34Phe), rs1940952445, ClinGen CA385227711, ClinVar RCV001916016, TOPMed rs1940952445, REVEL 0.30, ESM-1b 0.12, Uncertain significance, Early-infantile DEE
- L34P (p.Leu34Pro), gnomAD rs1228455370, REVEL 0.39, ESM-1b 0.00
- L34L (p.Leu34Leu), rs369386960, gnomAD 12-51662919-C-T, CADD 10.40
- K35* (p.Lys35Ter), TOPMed rs1555214275
- K35E (p.Lys35Glu), TOPMed rs1555214275, REVEL 0.55, ESM-1b 1.00
- K36* (p.Lys36Ter), Ensembl rs1555214276
- K36E (p.Lys36Glu), gnomAD 12-51662923-A-G, REVEL 0.47, ESM-1b 0.00
- P37L (p.Pro37Leu), TOPMed rs1339579428, gnomAD rs1339579428, REVEL 0.41, ESM-1b 0.15
- P37R (p.Pro37Arg), TOPMed rs1339579428, gnomAD rs1339579428, REVEL 0.34, ESM-1b 1.00
- P38L (p.Pro38Leu), gnomAD rs1227415655, REVEL 0.28, ESM-1b 0.00
- P38T (p.Pro38Thr), Ensembl rs1940952941, REVEL 0.37, ESM-1b 0.00
- K39* (p.Lys39Ter), Ensembl rs1555214280
- K39N (p.Lys39Asn), rs1940953152, ClinGen CA385227798, ClinVar RCV001326362, Ensembl rs1940953152, ESM-1b 0.00, AlphaMissense 0.65, Uncertain significance, Early-infantile DEE
- A40V (p.Ala40Val), rs2138671122, ClinGen CA385227814, ClinVar RCV001893999, Ensembl rs2138671122, ESM-1b 0.00, AlphaMissense 0.10, Uncertain significance, Early-infantile DEE
- A40A (p.Ala40Ala), rs145881860, gnomAD 12-51662937-C-T, CADD 3.60
- D41N (p.Asp41Asn), rs759888153, NCI-TCGA Cosmic COSV6197, cosmic curated COSV61975, ExAC rs759888153, REVEL 0.47, ESM-1b 0.00, Variant assessed as somatic; moderate impact.
- D41Y (p.Asp41Tyr), ExAC rs759888153, TOPMed rs759888153, gnomAD rs759888153, REVEL 0.56, ESM-1b 0.15
- G42G (p.Gly42Gly), gnomAD 12-51662943-C-T, CADD 13.50
- S43R (p.Ser43Arg), TOPMed rs1265928949, REVEL 0.49, ESM-1b 0.00
- S43S (p.Ser43Ser), gnomAD 12-51662946-T-C, CADD 9.07
- H44Y (p.His44Tyr), gnomAD 12-51662947-C-T, REVEL 0.38, ESM-1b 0.00
- H44R (p.His44Arg), gnomAD 12-51662948-A-G, REVEL 0.50, ESM-1b 0.00
- H44H (p.His44His), gnomAD 12-51662949-T-C, CADD 7.45
- R45Q (p.Arg45Gln), rs775601133, ClinGen CA318311, ClinVar RCV000189295, ExAC rs775601133, REVEL 0.52, ESM-1b 0.00, Likely benign, not provided
- R45W (p.Arg45Trp), rs373541157, ClinGen CA6570998, ClinVar RCV002275873, ClinVar RCV005058214, REVEL 0.67, ESM-1b 0.00, Uncertain significance, Early-infantile DEE; not provided
- R45R (p.Arg45Arg), rs1465422536, gnomAD 12-51662952-G-C, CADD 12.30
- E46* (p.Glu46Ter), Ensembl rs1555214285
- E46E (p.Glu46Glu), rs762950003, gnomAD 12-51662955-G-A, CADD 6.97
- D47G (p.Asp47Gly), ExAC rs764608088, gnomAD rs764608088, REVEL 0.60, ESM-1b 0.00
- D47N (p.Asp47Asn), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10063, REVEL 0.31, ESM-1b 0.00, Variant assessed as somatic; moderate impact.
- D47D (p.Asp47Asp), rs149013279, gnomAD 12-51662958-C-T, CADD 6.71
- D48N (p.Asp48Asn), rs757582223, ClinGen CA6571001, ClinVar RCV000489713, ClinVar RCV003766744, REVEL 0.44, ESM-1b 0.00, Uncertain significance, not provided; Early-infantile DEE
- D48D (p.Asp48Asp), rs767914121, gnomAD 12-51662961-T-C, CADD 10.90
- E49* (p.Glu49Ter), Ensembl rs1555214290
- E49A (p.Glu49Ala), TOPMed rs1033204733, REVEL 0.64, ESM-1b 0.85
- E49D (p.Glu49Asp), TOPMed rs1940954332, gnomAD rs1940954332, REVEL 0.24, ESM-1b 0.00
- E49E (p.Glu49Glu), rs1940954332, gnomAD 12-51662964-G-A, CADD 9.49
- D50Y (p.Asp50Tyr), gnomAD 12-51662965-G-T, REVEL 0.56, ESM-1b 1.00
- D50V (p.Asp50Val), gnomAD 12-51662966-A-T, REVEL 0.54, ESM-1b 0.96
- D50G (p.Asp50Gly), gnomAD 12-51662966-A-G, REVEL 0.53, ESM-1b 0.00
- S51R (p.Ser51Arg), Ensembl rs2138671231, REVEL 0.40, ESM-1b 0.54
- K52* (p.Lys52Ter), Ensembl rs1555214295
- K52K (p.Lys52Lys), rs1309308977, gnomAD 12-51662973-G-A, CADD 10.80
- P53R (p.Pro53Arg), rs1057524711, ClinGen CA16606300, ClinVar RCV000425482, ClinVar RCV002522709, REVEL 0.62, ESM-1b 1.00, Uncertain significance, not provided; Early-infantile DEE
- P53S (p.Pro53Ser), rs1940954610, ClinGen CA385228088, ClinVar RCV001349710, Ensembl rs1940954610, ESM-1b 1.00, AlphaMissense 0.35, Uncertain significance, Early-infantile DEE
- P53T (p.Pro53Thr), gnomAD 12-51662974-C-A, REVEL 0.65, ESM-1b 1.00
- P53P (p.Pro53Pro), rs750806532, gnomAD 12-51662976-C-T, CADD 12.00
- K54* (p.Lys54Ter), ExAC rs755721954, gnomAD rs755721954, Uncertain significance
- K54E (p.Lys54Glu), ExAC rs755721954, gnomAD rs755721954, REVEL 0.58, ESM-1b 1.00, Uncertain significance
- K54Q (p.Lys54Gln), rs755721954, ClinGen CA6571004, ClinVar RCV001089739, ExAC rs755721954, REVEL 0.46, ESM-1b 1.00, Uncertain significance, Developmental and epileptic encephalopathy, 13
- K54K (p.Lys54Lys), rs779576167, gnomAD 12-51662979-G-A, CADD 11.30
- N56K (p.Asn56Lys), rs1940955072, ClinGen CA385228130, ClinVar RCV002265321, Ensembl rs1940955072, ESM-1b 0.83, AlphaMissense 0.92, Uncertain significance, not provided
- N56N (p.Asn56Asn), rs1940955072, gnomAD 12-51662985-C-T, AlphaMissense 0.92, MetaLR 0.82
- S57S (p.Ser57Ser), rs748773097, gnomAD 12-51662988-C-T, CADD 11.50
- D58N (p.Asp58Asn), rs1940955246, cosmic curated COSV61989, UniProt VAR 076598, Ensembl rs1940955246, REVEL 0.79, ESM-1b 1.00, Uncertain significance, not provided
- D58D (p.Asp58Asp), gnomAD 12-51662991-C-T, CADD 11.80
- L59L (p.Leu59Leu), rs147027699, gnomAD 12-51662994-G-A, CADD 12.20
- E60* (p.Glu60Ter), Ensembl rs1555214310
- E60D (p.Glu60Asp), ExAC rs778905289, gnomAD rs778905289, REVEL 0.71, ESM-1b 1.00
- A61V (p.Ala61Val), rs2138671327, ClinGen CA385228198, ClinVar RCV001776773, Ensembl rs2138671327, ESM-1b 1.00, AlphaMissense 0.46, Uncertain significance, not provided
- K63* (p.Lys63Ter), Ensembl rs1555214311
- S64N (p.Ser64Asn), rs2540119566, ClinGen CA385228238, ClinVar RCV003754595, ClinVar RCV005230546, ESM-1b 0.00, AlphaMissense 0.09, Uncertain significance, Early-infantile DEE; Inborn genetic diseases; not provided
- S64G (p.Ser64Gly), gnomAD 12-51663007-A-G, REVEL 0.33, ESM-1b 0.63
- L65* (p.Leu65Ter), Ensembl rs1555214313
- L65L (p.Leu65Leu), rs748136961, gnomAD 12-51663012-G-A, CADD 11.60
- P66H (p.Pro66His), rs1940955829, ClinGen CA385228265, ClinVar RCV001198519, Ensembl rs1940955829, ESM-1b 1.00, AlphaMissense 0.99, Uncertain significance, Developmental and epileptic encephalopathy, 13
- P66R (p.Pro66Arg), rs1940955829, ClinGen CA385228267, ClinVar RCV001799961, Ensembl rs1940955829, ESM-1b 1.00, AlphaMissense 0.99, Uncertain significance, not provided
- I68V (p.Ile68Val), rs797045945, ClinGen CA205121, cosmic curated COSV61976, ClinVar RCV000192357, ESM-1b 0.00, AlphaMissense 0.60, Conflicting interpretations, Early-infantile DEE; not specified
- I68M (p.Ile68Met), gnomAD 12-51663021-C-G, REVEL 0.72, ESM-1b 0.00
- Y69Y (p.Tyr69Tyr), rs532501146, gnomAD 12-51663024-C-T, CADD 2.01
- G70R (p.Gly70Arg), rs1313776714, ClinGen CA385228318, ClinVar RCV000521808, gnomAD rs1313776714, REVEL 0.89, ESM-1b 1.00, Uncertain significance, not provided
- G70A (p.Gly70Ala), gnomAD 12-51663026-G-C, REVEL 0.86, ESM-1b 1.00
- G70G (p.Gly70Gly), gnomAD 12-51663027-G-C, CADD 12.50
- D71E (p.Asp71Glu), rs888638528, ClinGen CA385228340, ClinVar RCV001040218, ClinVar RCV005268860, ESM-1b 0.16, AlphaMissense 0.55, Uncertain significance, Developmental and epileptic encephalopathy; Inborn genetic diseases
- D71A (p.Asp71Ala), gnomAD 12-51663029-A-C, REVEL 0.93, ESM-1b 1.00
- D71D (p.Asp71Asp), rs888638528, gnomAD 12-51663030-C-T, AlphaMissense 0.55, MetaLR 0.74
- I72N (p.Ile72Asn), NCI-TCGA Cosmic COSV6199, cosmic curated COSV61994, REVEL 0.62, ESM-1b 1.00, Variant assessed as somatic; moderate impact.
- P73L (p.Pro73Leu), rs1592363476, ClinGen CA385228368, NCI-TCGA Cosmic COSV1006, cosmic curated COSV10063, ESM-1b 1.00, AlphaMissense 0.91, Uncertain significance, Developmental and epileptic encephalopathy
- P73S (p.Pro73Ser), rs2540119660, ClinGen CA385228362, ClinVar RCV003753740, ESM-1b 1.00, AlphaMissense 0.75, Uncertain significance, Early-infantile DEE
- P73P (p.Pro73Pro), gnomAD 12-51663036-C-T, CADD 7.05
- L76L (p.Leu76Leu), rs1259295421, gnomAD 12-51663043-C-T, CADD 11.40
- V77A (p.Val77Ala), ExAC rs773094980, gnomAD rs773094980, REVEL 0.50, ESM-1b 0.97
- V77I (p.Val77Ile), Ensembl rs1940956521, ESM-1b 0.00, AlphaMissense 0.11
- A78S (p.Ala78Ser), ExAC rs746834655, gnomAD rs746834655, REVEL 0.49, ESM-1b 0.00
- A78A (p.Ala78Ala), rs769994874, gnomAD 12-51663051-A-G, CADD 4.58
- V79F (p.Val79Phe), ExAC rs775593096, TOPMed rs775593096, gnomAD rs775593096, REVEL 0.53, ESM-1b 1.00, Uncertain significance
- V79I (p.Val79Ile), rs775593096, ClinGen CA6571014, ClinVar RCV001879953, ClinVar RCV004799402, REVEL 0.36, ESM-1b 0.14, Uncertain significance, Early-infantile DEE; Seizures, benign familial infantile, 5
- V79V (p.Val79Val), gnomAD 12-51663054-T-C, CADD 10.30
- P80L (p.Pro80Leu), NCI-TCGA TCGA novel, ESM-1b 1.00, AlphaMissense 0.92, Variant assessed as somatic; moderate impact.
- P80P (p.Pro80Pro), rs1266385723, gnomAD 12-51663057-C-G, CADD 12.50
- L81L (p.Leu81Leu), rs1940957150, gnomAD 12-51663058-C-T, CADD 9.41
- E82* (p.Glu82Ter), rs1555214322, NCI-TCGA Cosmic COSV6198, cosmic curated COSV61989, Ensembl rs1555214322, Variant assessed as somatic; high impact.
- F84F (p.Phe84Phe), rs1940957313, gnomAD 12-51663069-T-C, CADD 13.40
- Y87* (p.Tyr87Ter), rs1484586967, ClinGen CA385228549, ClinVar RCV000782050, TOPMed rs1484586967, Likely benign
- Y87C (p.Tyr87Cys), rs2138671507, ClinGen CA385228544, ClinVar RCV001755637, ClinVar RCV005095090, ESM-1b 1.00, AlphaMissense 0.61, Uncertain significance, Early-infantile DEE; not provided
- Y87Y (p.Tyr87Tyr), rs1484586967, gnomAD 12-51663078-C-T, CADD 9.95
- Y88C (p.Tyr88Cys), TOPMed rs1395637241, gnomAD rs1395637241, REVEL 0.96, ESM-1b 1.00
- L89* (p.Leu89Ter), Ensembl rs1555214324
- L89V (p.Leu89Val), TOPMed rs1168281350, gnomAD rs1168281350, REVEL 0.24, ESM-1b 0.00
- L89L (p.Leu89Leu), gnomAD 12-51663082-T-C, CADD 11.50
- T90K (p.Thr90Lys), ExAC rs763078635, TOPMed rs763078635, gnomAD rs763078635, ESM-1b 0.00, AlphaMissense 0.21, Uncertain significance
- T90M (p.Thr90Met), rs763078635, ClinGen CA6571015, cosmic curated COSV61995, ClinVar RCV001070120, REVEL 0.52, ESM-1b 0.50, Uncertain significance, SCN8A-related disorder; Early-infantile DEE
- T90R (p.Thr90Arg), rs763078635, ClinGen CA385228585, ClinVar RCV003754154, ESM-1b 0.00, AlphaMissense 0.28, Uncertain significance, Early-infantile DEE
- T90S (p.Thr90Ser), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10063, ESM-1b 0.00, AlphaMissense 0.07, Variant assessed as somatic; moderate impact.
- T90T (p.Thr90Thr), rs371712630, gnomAD 12-51663087-G-A, CADD 10.50
- Q91H (p.Gln91His), rs1017697457, ClinGen CA385215542, ClinVar RCV002891789, ESM-1b 1.00, AlphaMissense 0.42, Uncertain significance, Inborn genetic diseases; Early-infantile DEE
- Q91K (p.Gln91Lys), ExAC rs762256592, gnomAD rs762256592, REVEL 0.49, ESM-1b 1.00
- Q91L (p.Gln91Leu), rs768040823, ClinGen CA6571018, ClinVar RCV003591019, ExAC rs768040823, REVEL 0.69, ESM-1b 1.00, Uncertain significance, Early-infantile DEE
- Q91Q (p.Gln91Gln), rs1017697457, gnomAD 12-51663090-G-A, CADD 10.40
- K92* (p.Lys92Ter), Ensembl rs1555214325
- K92Q (p.Lys92Gln), rs1555214325, ClinGen CA385215544, ClinVar RCV003591016, ESM-1b 1.00, AlphaMissense 0.37, Uncertain significance, Early-infantile DEE
- K92R (p.Lys92Arg), Ensembl rs2138671593, REVEL 0.90, ESM-1b 0.00
- K92K (p.Lys92Lys), rs940189587, gnomAD 12-51663093-A-G, CADD 18.30
- T93S (p.Thr93Ser), TOPMed rs1483873062, gnomAD rs1483873062, REVEL 0.87, ESM-1b 1.00
- T93A (p.Thr93Ala), gnomAD 12-51684174-A-G, REVEL 0.94, ESM-1b 1.00
- T93N (p.Thr93Asn), gnomAD 12-51684175-C-A, REVEL 0.83, ESM-1b 1.00
- T93T (p.Thr93Thr), rs2138707894, gnomAD 12-51684176-C-T, CADD 15.10
- F94L (p.Phe94Leu), gnomAD 12-51684176-CT-C, CADD 29.40
- F94I (p.Phe94Ile), gnomAD 12-51684177-T-A, REVEL 0.93, ESM-1b 1.00
Public SCN8A analysis runs
- SCN8A analysis run — SCN8A (2,504 variants) — completed 2026-06-05
- SCN8A analysis run — SCN8A (2,504 variants) — completed 2026-05-27