CACNA1S (Q13698) variants and mutations
CACNA1S (also known as Q13698) is a human protein-coding gene encoding a voltage-dependent L-type calcium channel subunit alpha-1S protein. Its voltage sensing in skeletal-muscle transverse tubules mechanically activates RYR1 and couples membrane depolarization to sarcoplasmic-reticulum calcium release. Pathogenic variants can cause hypokalemic periodic paralysis, malignant-hyperthermia susceptibility, and congenital myopathy. This analysis covers 3,037 CACNA1S variants and mutations. Of these, 70% have computational variant effect predictions. Disease context includes hypokalemic periodic paralysis, type 1, congenital myopathy 18, and malignant hyperthermia of anesthesia. Example CACNA1S variants include M1V, E2*, and S4Y.
Variant analysis overview
- Gene: CACNA1S
- Protein: Q13698
- UniProt accession: Q13698
- Organism: Homo sapiens
- Variants analyzed: 3037
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 2,843 unspecified-consequence records; 2 stop lost; 91 missense variants; 78 synonymous variants; 1 in-frame deletions; 15 frameshift variants; 4 stop-gained variants; 2 splice-region variants; 1 substitution
- Prediction scores: 2,136 variants have prediction scores (70% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: hypokalemic periodic paralysis, type 1, congenital myopathy 18, malignant hyperthermia of anesthesia, hypertensive disorder, epilepsy, Hypertension, coronary artery disorder, Prinzmetal angina, neuropathic pain, fibromyalgia, Seizure, angina pectoris.
Protein structure and variant hotspots
- Protein features: 24 transmembrane segments; 3 binding sites; 8 post-translational modification sites.
- Structural context: 699 variants have structural context.
- PTM context: 7 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, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable CACNA1S variants
Examples include M1V, E2*, S4Y, S5L, S5P, Q7*, D8V, E9*. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1V (p.Met1Val), rs201803122, ClinGen CA078742, ClinVar RCV001216369, ClinVar RCV005012623, MetaLR 0.90, MetaSVM 0.21, Uncertain significance, Thyrotoxic periodic paralysis, susceptibility to, 1; Congenital myopathy 18; Hyp
- E2* (p.Glu2Ter), Ensembl rs1553254312
- S4Y (p.Ser4Tyr), Ensembl rs1663158375, REVEL 0.34, CADD 23.90
- S5L (p.Ser5Leu), rs772738139, ClinGen CA078271, ClinVar RCV001221566, ClinVar RCV002491692, REVEL 0.29, CADD 23.70, Uncertain significance, Congenital myopathy 18; Hypokalemic periodic paralysis, type 1; Thyrotoxic perio
- S5P (p.Ser5Pro), 1000Genomes rs201601955, ExAC rs201601955, gnomAD rs201601955, REVEL 0.31, CADD 22.60
- Q7* (p.Gln7Ter), rs374950276, ClinGen CA078741, ClinVar RCV001060025, ESP rs374950276, Pathogenic
- D8V (p.Asp8Val), gnomAD rs921008103, REVEL 0.44, CADD 25.00
- E9* (p.Glu9Ter), Ensembl rs1553254305
- E9A (p.Glu9Ala), rs761386471, ClinGen CA344158720, ClinVar RCV004013286, AlphaMissense 0.14, MetaLR 0.84, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- E9V (p.Glu9Val), ExAC rs761386471, gnomAD rs761386471, REVEL 0.47, AlphaMissense 0.14
- G10D (p.Gly10Asp), rs1663157502, ClinGen CA344158691, ClinVar RCV001914062, NCI-TCGA TCGA novel, REVEL 0.26, CADD 19.80, Uncertain significance, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- G10S (p.Gly10Ser), rs371905958, ClinGen CA079364, ClinVar RCV004015759, ClinVar RCV004801433, REVEL 0.21, CADD 19.40, Uncertain significance, Malignant hyperthermia, susceptibility to, 5; not provided
- L11P (p.Leu11Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L11R (p.Leu11Arg), rs1420388292, ClinGen CA344158674, ClinVar RCV003217186, ClinVar RCV003779707, REVEL 0.38, CADD 13.90, Conflicting interpretations, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- K13* (p.Lys13Ter), Ensembl rs1553254302
- K14* (p.Lys14Ter), Ensembl rs1553254297
- Q15* (p.Gln15Ter), TOPMed rs1553254296
- Q15H (p.Gln15His), gnomAD rs1412221314, REVEL 0.43, CADD 23.60
- P16L (p.Pro16Leu), rs768611153, ClinGen CA083598, ClinVar RCV002624398, ClinVar RCV005415658, REVEL 0.31, CADD 22.70, Conflicting interpretations, not provided; Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic
- P16R (p.Pro16Arg), ExAC rs768611153, TOPMed rs768611153, gnomAD rs768611153, Likely benign
- P16S (p.Pro16Ser), TOPMed rs991515094
- K17* (p.Lys17Ter), Ensembl rs1553254290
- K17N (p.Lys17Asn), NCI-TCGA Cosmic COSV6293, cosmic curated COSV62938, Variant assessed as somatic; moderate impact.
- K17R (p.Lys17Arg), Ensembl rs1663155549
- K18* (p.Lys18Ter), Ensembl rs1553254289
- K18R (p.Lys18Arg), gnomAD rs1663155244, REVEL 0.44, CADD 24.00
- V20I (p.Val20Ile), rs2464701778, ClinGen CA344158395, ClinVar RCV003786493, Uncertain significance, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- P21S (p.Pro21Ser), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10075, REVEL 0.14, CADD 21.60, Variant assessed as somatic; moderate impact.
- E22* (p.Glu22Ter), Ensembl rs1553254287
- E22A (p.Glu22Ala), rs745835, ClinGen CA344158339, ClinVar RCV004014154, AlphaMissense 0.13, MetaLR 0.08, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- E22D (p.Glu22Asp), NCI-TCGA Cosmic COSV6294, cosmic curated COSV62944, REVEL 0.06, CADD 11.00, Variant assessed as somatic; moderate impact.
- E22V (p.Glu22Val), Ensembl rs745835
- I23L (p.Ile23Leu), gnomAD rs1202505813, REVEL 0.11, CADD 8.81
- R26S (p.Arg26Ser), NCI-TCGA TCGA novel, REVEL 0.21, CADD 23.10, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- P27A (p.Pro27Ala), TOPMed rs1663154092
- P28H (p.Pro28His), cosmic curated COSV62945, ExAC rs747041937, gnomAD rs747041937, REVEL 0.30, CADD 27.70, Uncertain significance
- P28L (p.Pro28Leu), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10075, NCI-TCGA Cosmic COSV6294, Variant assessed as somatic; moderate impact.
- P28R (p.Pro28Arg), ExAC rs747041937, gnomAD rs747041937, REVEL 0.25, CADD 26.80, Uncertain significance, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- P28S (p.Pro28Ser), rs1297380219, ClinGen CA344158177, cosmic curated COSV62939, ClinVar RCV004014974, REVEL 0.08, AlphaMissense 0.10, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- P28T (p.Pro28Thr), rs1297380219, ClinGen CA344158185, ClinVar RCV002265455, ClinVar RCV003774834, AlphaMissense 0.10, MetaLR 0.20, Uncertain significance, Malignant hyperthermia, susceptibility to, 5; not provided; Hypokalemic periodic
- R29G (p.Arg29Gly), rs577022740, ClinGen CA344158162, ClinVar RCV002046700, 1000Genomes rs577022740, REVEL 0.52, CADD 24.00, Uncertain significance, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- R29L (p.Arg29Leu), rs758594181, ClinGen CA344158157, ClinVar RCV004015056, NCI-TCGA Cosmic COSV6293, REVEL 0.61, CADD 27.90, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- R29P (p.Arg29Pro), ExAC rs758594181, TOPMed rs758594181, gnomAD rs758594181, Benign
- R29Q (p.Arg29Gln), rs758594181, ClinGen CA084025, NCI-TCGA Cosmic COSV6293, cosmic curated COSV62935, REVEL 0.43, CADD 28.40, Conflicting interpretations, not provided; Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic
- R29W (p.Arg29Trp), rs577022740, ClinGen CA084021, cosmic curated COSV62937, ClinVar RCV001367207, REVEL 0.53, CADD 25.00, Conflicting interpretations, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- A30D (p.Ala30Asp), Ensembl rs1663151776
- A30P (p.Ala30Pro), gnomAD rs1663151908, REVEL 0.32, CADD 24.30
- L31* (p.Leu31Ter), Ensembl rs1553254283
- L31F (p.Leu31Phe), rs556751671, 1000Genomes rs556751671, ExAC rs556751671, TOPMed rs556751671, REVEL 0.55, CADD 23.70, Conflicting interpretations, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- C33* (p.Cys33Ter), ESP rs377020349, gnomAD rs377020349, CADD 37.00
- C33R (p.Cys33Arg), TOPMed rs1291268307, Uncertain significance, not provided
- C33Y (p.Cys33Tyr), gnomAD rs1488054866
- L34Q (p.Leu34Gln), ExAC rs754333173, gnomAD rs754333173
- L34V (p.Leu34Val), rs1408297288, ClinGen CA344157983, ClinVar RCV003809494, ClinVar RCV006548902, REVEL 0.24, CADD 21.50, Uncertain significance, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- T35A (p.Thr35Ala), rs1663150760, ClinGen CA344157957, ClinVar RCV001883625, TOPMed rs1663150760, AlphaMissense 0.17, MetaLR 0.13, Uncertain significance, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- T35I (p.Thr35Ile), rs2464701502, NCI-TCGA Cosmic COSV1007, cosmic curated COSV10075, ClinGen CA344157946, REVEL 0.26, CADD 24.80, Uncertain significance, not specified; Malignant hyperthermia, susceptibility to, 5
- T35P (p.Thr35Pro), rs1663150760, ClinGen CA344157959, ClinVar RCV002922319, ClinVar RCV006251167, REVEL 0.26, AlphaMissense 0.17, Uncertain significance, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- E37* (p.Glu37Ter), Ensembl rs1553254279
- E37K (p.Glu37Lys), Ensembl rs1553254279
- N38D (p.Asn38Asp), rs2464701476, ClinGen CA344157889, ClinVar RCV004012776, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- N38K (p.Asn38Lys), rs756619964, ClinGen CA077975, ClinVar RCV001307108, ClinVar RCV004005041, REVEL 0.70, CADD 25.80, Uncertain significance, Inborn genetic diseases; Malignant hyperthermia, susceptibility to, 5; Hypokalem
- N38T (p.Asn38Thr), Ensembl rs1572080650
- N38Y (p.Asn38Tyr), rs2464701476, ClinGen CA344157893, ClinVar RCV003809075, Uncertain significance, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- P39L (p.Pro39Leu), rs1663146674, ClinGen CA344157834, ClinVar RCV001313085, Ensembl rs1663146674, REVEL 0.62, CADD 29.70, Uncertain significance, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- P39S (p.Pro39Ser), rs749891107, ClinGen CA344157857, ClinVar RCV004012357, REVEL 0.69, CADD 27.80, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- P39T (p.Pro39Thr), ExAC rs749891107, gnomAD rs749891107, REVEL 0.66, CADD 27.10
- L40P (p.Leu40Pro), NCI-TCGA Cosmic COSV6293, cosmic curated COSV62938, Variant assessed as somatic; moderate impact.
- L40V (p.Leu40Val), TOPMed rs1663146474, REVEL 0.07, CADD 9.05
- R41K (p.Arg41Lys), rs2464701413, ClinGen CA344157794, ClinVar RCV004014474, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- K42* (p.Lys42Ter), rs1553254275, ClinGen CA344157756, ClinVar RCV003787594, ClinVar RCV006264146, CADD 56.00, Pathogenic
- K42N (p.Lys42Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A43T (p.Ala43Thr), NCI-TCGA Cosmic COSV6294, cosmic curated COSV62941, REVEL 0.16, CADD 23.60, Variant assessed as somatic; moderate impact.
- C44* (p.Cys44Ter), Ensembl rs1553254274
- I45N (p.Ile45Asn), rs2464701347, ClinGen CA344157656, ClinVar RCV004015995, REVEL 0.34, CADD 26.90, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- I45V (p.Ile45Val), Ensembl rs2102193812, Uncertain significance, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- S46G (p.Ser46Gly), rs773923999, ClinGen CA344157633, ClinVar RCV004013089, ClinVar RCV005220831, REVEL 0.16, CADD 19.00, Conflicting interpretations, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- S46R (p.Ser46Arg), rs773923999, ClinGen CA078166, ClinVar RCV002610699, ClinVar RCV006546374, REVEL 0.18, CADD 19.50, Uncertain significance, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- I47N (p.Ile47Asn), rs372497364, ClinGen CA078231, ClinVar RCV001245317, ClinVar RCV005532899, REVEL 0.74, CADD 25.90, Conflicting interpretations, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- I47T (p.Ile47Thr), rs372497364, ClinGen CA36018221, ClinVar RCV001899114, 1000Genomes rs372497364, REVEL 0.70, CADD 24.70, Likely benign, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- V48A (p.Val48Ala), rs977298165, ClinGen CA36018215, ClinVar RCV001054284, ClinVar RCV003455242, REVEL 0.54, CADD 25.20, Conflicting interpretations, Congenital myopathy 18; Hypokalemic periodic paralysis, type 1; Malignant hypert
- E49* (p.Glu49Ter), Ensembl rs1553254270
- W50* (p.Trp50Ter), NCI-TCGA Cosmic COSV6294, cosmic curated COSV62941, Ensembl rs2102193774, Variant assessed as somatic; high impact.
- W50C (p.Trp50Cys), rs1553254269, ClinGen CA344157522, ClinVar RCV003792830, Uncertain significance, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- W50R (p.Trp50Arg), rs574267605, ClinGen CA078261, ClinVar RCV003328731, ClinVar RCV005227997, REVEL 0.81, CADD 26.70, Uncertain significance, not provided; Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic
- K51* (p.Lys51Ter), Ensembl rs1553254268
- P52L (p.Pro52Leu), cosmic curated COSV62939, gnomAD rs1272670603, REVEL 0.43, CADD 24.20
- P52T (p.Pro52Thr), rs2464692224, ClinGen CA344156308, ClinVar RCV003481583, Uncertain significance, not provided
- F53L (p.Phe53Leu), rs754668127, ClinGen CA078416, cosmic curated COSV62941, ClinVar RCV002004642, REVEL 0.72, CADD 23.00, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- E54* (p.Glu54Ter), Ensembl rs1553254121, Uncertain significance
- E54D (p.Glu54Asp), rs569061608, ClinGen CA078492, ClinVar RCV001054828, ClinVar RCV002481993, REVEL 0.47, CADD 22.60, Uncertain significance, Thyrotoxic periodic paralysis, susceptibility to, 1; Hypokalemic periodic paraly
- E54K (p.Glu54Lys), rs1553254121, NCI-TCGA Cosmic COSV6293, cosmic curated COSV62939, AlphaMissense 0.52, MetaLR 0.68, Uncertain significance, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- E54Q (p.Glu54Gln), rs1553254121, ClinGen CA344156269, NCI-TCGA Cosmic COSV6293, cosmic curated COSV62938, AlphaMissense 0.52, MetaLR 0.68, Uncertain significance, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- T55K (p.Thr55Lys), 1000Genomes rs549107212, ExAC rs549107212, TOPMed rs549107212, gnomAD rs549107212, REVEL 0.11, CADD 22.30, Likely benign
- T55M (p.Thr55Met), rs549107212, ClinGen CA078498, NCI-TCGA Cosmic COSV6294, cosmic curated COSV62940, REVEL 0.07, CADD 22.00, Conflicting interpretations, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- I56L (p.Ile56Leu), ESP rs373778743
- I57F (p.Ile57Phe), Ensembl rs1663048287, REVEL 0.85, CADD 28.90, Uncertain significance
- I57M (p.Ile57Met), rs1558090893, ClinGen CA344156213, NCI-TCGA Cosmic COSV1007, cosmic curated COSV10075, REVEL 0.67, CADD 26.40, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- I57V (p.Ile57Val), rs1663048287, ClinGen CA344156226, ClinVar RCV001886111, Ensembl rs1663048287, REVEL 0.40, CADD 26.30, Uncertain significance, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- L58* (p.Leu58Ter), Ensembl rs1553254119
- I61V (p.Ile61Val), rs147382463, ClinGen CA078582, ClinVar RCV003104780, ClinVar RCV004725634, REVEL 0.67, CADD 26.00, Conflicting interpretations, not provided; Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic
- F62S (p.Phe62Ser), rs2464691872, ClinGen CA344156132, ClinVar RCV003404775, Uncertain significance, not specified
- A63P (p.Ala63Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A63S (p.Ala63Ser), rs886045804, ClinGen CA10609409, ClinVar RCV000397333, Ensembl rs886045804, REVEL 0.29, CADD 25.90, Uncertain significance, Hypokalemic periodic paralysis, type 1
- A63V (p.Ala63Val), Ensembl rs769486088, Uncertain significance, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- A63D (p.Ala63Asp), rs886045804, Uncertain significance
- N64D (p.Asn64Asp), Ensembl rs1663047287, REVEL 0.83, CADD 27.90
- N64S (p.Asn64Ser), ExAC rs773106413, gnomAD rs773106413, REVEL 0.71, CADD 27.10, Uncertain significance, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- C65* (p.Cys65Ter), Ensembl rs1553254117
- C65Y (p.Cys65Tyr), TOPMed rs1298264664, gnomAD rs1298264664, REVEL 0.93, CADD 26.90
- V66A (p.Val66Ala), rs1663046954, ClinGen CA344156057, ClinVar RCV001324361, ClinVar RCV004005122, REVEL 0.64, CADD 24.90, Uncertain significance, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- V66M (p.Val66Met), rs886045803, ClinGen CA10609408, ClinVar RCV000346607, Ensembl rs886045803, AlphaMissense 0.21, MetaLR 0.51, Uncertain significance, Hypokalemic periodic paralysis, type 1
- A67V (p.Ala67Val), rs1553254116, ClinGen CA344156038, ClinVar RCV000558890, Ensembl rs1553254116, REVEL 0.22, CADD 28.30, Uncertain significance, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- L68P (p.Leu68Pro), TOPMed rs1448468275, gnomAD rs1448468275, REVEL 0.92, CADD 28.80
- A69D (p.Ala69Asp), rs12406479, ClinGen CA36016792, ClinVar RCV001984515, ClinVar RCV003481201, REVEL 0.82, CADD 26.60, Uncertain significance, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- A69V (p.Ala69Val), rs12406479, ClinGen CA344155985, ClinVar RCV001100107, ClinVar RCV003769064, REVEL 0.78, CADD 26.90, Uncertain significance, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- A69G (p.Ala69Gly), rs12406479, ClinGen CA078793, cosmic curated COSV62939, ClinVar RCV000249964, REVEL 0.37, CADD 24.40, Benign, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- A69S (p.Ala69Ser), cosmic curated COSV62938, gnomAD rs1279858225, REVEL 0.63, CADD 25.60
- V70A (p.Val70Ala), rs747599178, ClinGen CA078806, ClinVar RCV001206104, ExAC rs747599178, REVEL 0.12, CADD 22.00, Uncertain significance, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- V70G (p.Val70Gly), ExAC rs747599178, TOPMed rs747599178, gnomAD rs747599178, Uncertain significance
- V70L (p.Val70Leu), rs771706267, NCI-TCGA Cosmic COSV6294, cosmic curated COSV62944, ExAC rs771706267, REVEL 0.06, CADD 21.00, Likely benign
- V70M (p.Val70Met), rs771706267, ClinGen CA078801, ClinVar RCV000436745, ClinVar RCV001088952, REVEL 0.05, CADD 21.60, Conflicting interpretations, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- L72P (p.Leu72Pro), ExAC rs778502465, gnomAD rs778502465, REVEL 0.82, CADD 27.40, Uncertain significance, Inborn genetic diseases
- P73L (p.Pro73Leu), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10075, Variant assessed as somatic; moderate impact.
- P73R (p.Pro73Arg), rs1194326701, ClinGen CA344155918, ClinVar RCV004015357, TOPMed rs1194326701, REVEL 0.94, CADD 27.90, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- P73S (p.Pro73Ser), rs2464691516, ClinGen CA344155923, ClinVar RCV004016798, NCI-TCGA Cosmic COSV6293, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- M74I (p.Met74Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- M74L (p.Met74Leu), NCI-TCGA Cosmic COSV6293, cosmic curated COSV62937, Variant assessed as somatic; moderate impact.
- M74V (p.Met74Val), rs2464691467, ClinGen CA344155915, ClinVar RCV004011840, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- P75L (p.Pro75Leu), rs779684649, ClinGen CA078901, cosmic curated COSV62943, ClinVar RCV000806923, REVEL 0.86, CADD 27.80, Uncertain significance, Congenital myopathy 18; Malignant hyperthermia, susceptibility to, 5; Thyrotoxic
- P75S (p.Pro75Ser), ExAC rs749003741, gnomAD rs749003741, REVEL 0.82, CADD 26.20, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- E76* (p.Glu76Ter), Ensembl rs1553254111
- D77E (p.Asp77Glu), gnomAD rs1436049839, REVEL 0.33, CADD 16.90
- D77G (p.Asp77Gly), rs1663045058, ClinGen CA344155834, ClinVar RCV003082322, ClinVar RCV004009403, REVEL 0.72, CADD 25.20, Uncertain significance, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- D78E (p.Asp78Glu), ExAC rs767375833, gnomAD rs767375833
- D78N (p.Asp78Asn), TOPMed rs1368099409, gnomAD rs1368099409
- D78Y (p.Asp78Tyr), TOPMed rs1368099409, gnomAD rs1368099409, REVEL 0.83, CADD 27.60, Uncertain significance, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- N79K (p.Asn79Lys), rs150180227, ClinGen CA078966, ClinVar RCV002766440, ESP rs150180227, REVEL 0.41, CADD 23.20, Likely benign, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- N80K (p.Asn80Lys), rs1663044259, ClinGen CA344155711, ClinVar RCV003121429, ClinVar RCV004009577, REVEL 0.51, CADD 25.20, Uncertain significance, not provided; Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic
- N80S (p.Asn80Ser), rs752667224, ClinGen CA078980, ClinVar RCV001903409, ClinVar RCV004010831, REVEL 0.56, CADD 25.20, Conflicting interpretations, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- S81A (p.Ser81Ala), rs1396542342, ClinGen CA344155704, ClinVar RCV004010027, gnomAD rs1396542342, REVEL 0.22, CADD 5.26, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- S81F (p.Ser81Phe), gnomAD rs1185207877, REVEL 0.28, CADD 20.30
- L82P (p.Leu82Pro), Ensembl rs2102190549, Uncertain significance, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- N83K (p.Asn83Lys), gnomAD rs1211791767, REVEL 0.77, CADD 24.70
- N83S (p.Asn83Ser), rs1663043526, ClinGen CA344155655, ClinVar RCV004012634, Ensembl rs1663043526, AlphaMissense 0.43, MetaLR 0.93, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- L84H (p.Leu84His), rs2464691162, ClinGen CA344155622, ClinVar RCV002811219, NCI-TCGA TCGA novel, Uncertain significance, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- L84V (p.Leu84Val), TOPMed rs1663043307, gnomAD rs1663043307, REVEL 0.17, CADD 8.83
- G85D (p.Gly85Asp), gnomAD rs1373413177, REVEL 0.52, CADD 17.00, Likely benign, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- G85S (p.Gly85Ser), rs369931782, ClinGen CA079052, ClinVar RCV000687088, ClinVar RCV000765033, REVEL 0.31, CADD 15.20, Conflicting interpretations, Inborn genetic diseases; Hypokalemic periodic paralysis, type 1; Malignant hyper
- E87=, NCI-TCGA Cosmic COSV6294, Variant assessed as somatic; low impact.
- E87K (p.Glu87Lys), ExAC rs774972928, gnomAD rs774972928, REVEL 0.79, CADD 33.00
- K88* (p.Lys88Ter), ESP rs140330831, ExAC rs140330831, TOPMed rs140330831, gnomAD rs140330831, Benign
- K88E (p.Lys88Glu), rs140330831, ClinGen CA079143, ClinVar RCV000651220, ClinVar RCV000729718, REVEL 0.56, CADD 24.30, Conflicting interpretations, Inborn genetic diseases; Hypokalemic periodic paralysis, type 1; not provided
- L89P (p.Leu89Pro), Ensembl rs2102167678
- E90* (p.Glu90Ter), Ensembl rs1553252962
- E90G (p.Glu90Gly), gnomAD rs1158143722, REVEL 0.97, CADD 32.00
- Y91D (p.Tyr91Asp), Ensembl rs1572064231
- Y91F (p.Tyr91Phe), rs1013152799, ClinGen CA35998528, ClinVar RCV001061814, ClinVar RCV002267071, REVEL 0.86, CADD 27.00, Uncertain significance, Congenital myopathy 18; not provided; Thyrotoxic periodic paralysis, susceptibil
- Y91H (p.Tyr91His), rs1572064231, ClinGen CA344145961, ClinVar RCV003783396, AlphaMissense 0.58, MetaLR 0.98, Uncertain significance, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- F92L (p.Phe92Leu), NCI-TCGA TCGA novel, Uncertain significance, not provided
- L94F (p.Leu94Phe), gnomAD rs1196842684, REVEL 0.76, CADD 24.00
- I95T (p.Ile95Thr), rs550479246, ClinGen CA079319, ClinVar RCV001957912, ClinVar RCV005006273, REVEL 0.40, CADD 22.80, Conflicting interpretations, not provided; Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic
- I95V (p.Ile95Val), rs1558082384, ClinGen CA344145849, ClinVar RCV004016220, Ensembl rs1558082384, REVEL 0.39, CADD 14.90, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- V96I (p.Val96Ile), cosmic curated COSV10889, Ensembl rs2102167629, REVEL 0.25, CADD 15.30
- F97L (p.Phe97Leu), NCI-TCGA Cosmic COSV6293, cosmic curated COSV62937, Variant assessed as somatic; moderate impact.
- S98* (p.Ser98Ter), gnomAD rs1310029541, Uncertain significance
- S98A (p.Ser98Ala), rs1196937008, ClinGen CA344145729, ClinVar RCV003208978, TOPMed rs1196937008, REVEL 0.39, AlphaMissense 0.07, Uncertain significance, Inborn genetic diseases
- S98L (p.Ser98Leu), rs1310029541, ClinGen CA344145692, ClinVar RCV003517867, ClinVar RCV006562602, REVEL 0.56, CADD 24.80, Conflicting interpretations, Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis, ty
- S98P (p.Ser98Pro), rs1196937008, ClinGen CA344145735, ClinVar RCV004012481, AlphaMissense 0.07, MetaLR 0.75, Uncertain significance, Malignant hyperthermia, susceptibility to, 5
- S98W (p.Ser98Trp), NCI-TCGA Cosmic COSV6293, cosmic curated COSV62939, Variant assessed as somatic; moderate impact.
- I99N (p.Ile99Asn), rs374127575, ClinGen CA079458, ClinVar RCV001304568, ESP rs374127575, AlphaMissense 0.76, MetaLR 0.98, Uncertain significance, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- E100* (p.Glu100Ter), Ensembl rs1298520651, Uncertain significance, in CMYO18
- E100K (p.Glu100Lys), rs1298520651, UniProt VAR 088226, Ensembl rs1298520651, REVEL 0.95, CADD 28.70, Uncertain significance, in CMYO18
- A101D (p.Ala101Asp), gnomAD rs1224046860, REVEL 0.87, CADD 25.60
- A101P (p.Ala101Pro), Ensembl rs1572064164
- A102S (p.Ala102Ser), rs753901380, ClinGen CA344145486, ClinVar RCV003070709, ClinVar RCV004808404, REVEL 0.28, CADD 16.20, Uncertain significance, Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility t
- A102T (p.Ala102Thr), rs753901380, ClinGen CA079500, NCI-TCGA Cosmic COSV6294, cosmic curated COSV62941, REVEL 0.23, CADD 21.30, Conflicting interpretations, Thyrotoxic periodic paralysis, susceptibility to, 1; Hypokalemic periodic paraly
- M103I (p.Met103Ile), NCI-TCGA Cosmic COSV6293, cosmic curated COSV62939, Variant assessed as somatic; moderate impact.
- K104* (p.Lys104Ter), Ensembl rs1553252953
- I105S (p.Ile105Ser), rs780307562, ClinGen CA079567, ClinVar RCV002044694, ClinVar RCV005627436, REVEL 0.98, CADD 29.00, Uncertain significance, not provided; Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic
- I106V (p.Ile106Val), Ensembl rs994967763
Public CACNA1S analysis runs
- CACNA1S analysis run — CACNA1S (3,037 variants) — completed 2026-08-18