CLCN1 (Chloride channel protein 1) variants and mutations
CLCN1 (also known as Chloride channel protein 1) is a human protein-coding gene encoding a chloride channel protein 1 protein. Its chloride conductance stabilizes the resting membrane potential of skeletal muscle and prevents repetitive firing after contraction. Loss-of-function variants cause myotonia congenita, with delayed muscle relaxation and stiffness. This analysis covers 1,686 CLCN1 variants and mutations. Of these, 72% have computational variant effect predictions. Disease context includes myotonia congenita, autosomal recessive, Thomsen and Becker disease, and Myotonia. Example CLCN1 variants include M1?, E2K, and E2A.
Variant analysis overview
- Gene: CLCN1
- Protein: Chloride channel protein 1
- UniProt accession: P35523
- Organism: Homo sapiens
- Variants analyzed: 1686
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 1,488 unspecified-consequence records; 80 missense variants; 1 in-frame deletions; 8 stop-gained variants; 79 synonymous variants; 14 frameshift variants; 1 in-frame insertions; 2 splice-region variants; 13 substitution
- Prediction scores: 1,219 variants have prediction scores (72% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: myotonia congenita, autosomal recessive, Thomsen and Becker disease, Myotonia, Tip-toe gait, hyperkalemic periodic paralysis, Abnormality of the musculature, Smith-Lemli-Opitz syndrome, hereditary disease, EMG: myotonic discharges, hypokalemic periodic paralysis, type 1, myocardial infarction, Vertigo.
Protein structure and variant hotspots
- Protein features: 5 transmembrane segments; 2 domains; 3 binding sites; 1 post-translational modification sites.
- Structural context: 376 variants have structural context.
- PTM context: 2 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 CLCN1 variants
Examples include M1?, E2K, E2A, p.Gln3 Ser4del, Q3*, Q3Q, S4F, S4P. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA Cosmic COSV1005, NCI-TCGA Cosmic COSV5837, Variant assessed as somatic; high impact.
- E2K (p.Glu2Lys), NCI-TCGA Cosmic COSV1005, REVEL 0.27, CADD 17.20, Variant assessed as somatic; moderate impact.
- E2A (p.Glu2Ala), gnomAD 7-143316217-A-C, REVEL 0.30, CADD 22.00
- p.Gln3 Ser4del, rs748679335, gnomAD 7-143316218-GCAAT, CADD 12.30
- Q3* (p.Gln3Ter), gnomAD 7-143316219-C-T, CADD 34.00
- Q3Q (p.Gln3Gln), rs555409185, gnomAD 7-143316221-A-G, CADD 0.23
- S4F (p.Ser4Phe), ExAC rs777366731, TOPMed rs777366731, gnomAD rs777366731, REVEL 0.34, CADD 15.30
- S4P (p.Ser4Pro), gnomAD 7-143316222-T-C, REVEL 0.52, CADD 6.90
- S4Y (p.Ser4Tyr), gnomAD 7-143316223-C-A, REVEL 0.34, CADD 17.30
- R5L (p.Arg5Leu), NCI-TCGA TCGA novel, 1000Genomes rs201327261, ExAC rs201327261, TOPMed rs201327261, REVEL 0.21, CADD 4.58, Uncertain significance
- R5Q (p.Arg5Gln), rs201327261, ClinGen CA4536799, ClinVar RCV003090936, ClinVar RCV005323329, REVEL 0.14, CADD 3.00, Uncertain significance, Inborn genetic diseases; Congenital myotonia, autosomal recessive form; Congenit
- R5W (p.Arg5Trp), rs1322496244, ClinGen CA369676375, ClinVar RCV000605421, ClinVar RCV001860307, REVEL 0.33, CADD 15.70, Conflicting interpretations, Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal do
- R5R (p.Arg5Arg), gnomAD 7-143316225-C-A, CADD 3.18
- S6L (p.Ser6Leu), TOPMed rs1802287844
- S6* (p.Ser6Ter), gnomAD 7-143316229-C-G, CADD 34.00
- Q7* (p.Gln7Ter), rs2487015049, ClinGen CA369676406, ClinVar RCV003794847, CADD 34.00, Pathogenic
- Q7Q (p.Gln7Gln), gnomAD 7-143316233-G-A, CADD 2.91
- Q8E (p.Gln8Glu), gnomAD 7-143316234-C-G, REVEL 0.19, CADD 1.37
- Q8H (p.Gln8His), gnomAD 7-143316236-G-C, REVEL 0.13, CADD 14.20
- Q8Q (p.Gln8Gln), rs150304865, gnomAD 7-143316236-G-A, CADD 2.90
- R9C (p.Arg9Cys), ExAC rs745344072, TOPMed rs745344072, gnomAD rs745344072, REVEL 0.22, CADD 16.70, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- R9H (p.Arg9His), rs115379077, ClinGen CA4536803, ClinVar RCV000266244, ClinVar RCV000429129, REVEL 0.13, CADD 0.11, Benign/Likely benign, not provided; Congenital myotonia, autosomal recessive form; Congenital myotonia
- R9P (p.Arg9Pro), 1000Genomes rs115379077, ESP rs115379077, ExAC rs115379077, TOPMed rs115379077, REVEL 0.17, CADD 0.22, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- R9S (p.Arg9Ser), rs745344072, ClinGen CA369676448, ClinVar RCV000817468, ExAC rs745344072, REVEL 0.13, CADD 8.71, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- R9L (p.Arg9Leu), gnomAD 7-143316238-G-T, REVEL 0.22, CADD 0.05
- R9R (p.Arg9Arg), rs1255585330, gnomAD 7-143316239-T-G, CADD 2.29
- G10R (p.Gly10Arg), gnomAD rs1051714088, REVEL 0.17, CADD 11.30
- G10W (p.Gly10Trp), gnomAD 7-143316240-G-T, REVEL 0.38, CADD 22.40
- G10V (p.Gly10Val), gnomAD 7-143316241-G-T, REVEL 0.32, CADD 18.10
- G10G (p.Gly10Gly), gnomAD 7-143316242-G-A, CADD 3.35
- G11A (p.Gly11Ala), rs1563071875, ClinGen CA369676500, ClinVar RCV000706459, TOPMed rs1563071875, REVEL 0.16, CADD 8.81, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- G11C (p.Gly11Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G11D (p.Gly11Asp), TOPMed rs1563071875, gnomAD rs1563071875, REVEL 0.21, CADD 9.71, Uncertain significance
- G11S (p.Gly11Ser), gnomAD rs1210604442, REVEL 0.15, CADD 1.03
- G11V (p.Gly11Val), NCI-TCGA Cosmic COSV5837, REVEL 0.16, CADD 10.20, Variant assessed as somatic; moderate impact.
- G11G (p.Gly11Gly), rs780696139, gnomAD 7-143316245-T-C, CADD 3.20
- E12K (p.Glu12Lys), Ensembl rs1802288634
- Q13K (p.Gln13Lys), rs143025648, ClinGen CA4536805, ClinVar RCV000478896, ClinVar RCV001202209, REVEL 0.15, CADD 13.80, Uncertain significance, Inborn genetic diseases; Congenital myotonia, autosomal recessive form; Congenit
- Q13P (p.Gln13Pro), Ensembl rs1802288781
- Q13* (p.Gln13Ter), gnomAD 7-143316249-C-T, CADD 34.00
- Q13H (p.Gln13His), rs1334449555, gnomAD 7-143316250-AAAGC, CADD 27.90
- S14R (p.Ser14Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- W15R (p.Trp15Arg), rs1194717455, TOPMed rs1194717455, gnomAD rs1194717455, ClinGen CA369676576, REVEL 0.56, CADD 25.40, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- W16* (p.Trp16Ter), rs769092535, ClinGen CA4536806, ClinVar RCV001868856, ClinVar RCV004546671, CADD 37.00, Pathogenic
- W16C (p.Trp16Cys), TOPMed rs1434585576, gnomAD rs1434585576, REVEL 0.63, CADD 26.70
- G17D (p.Gly17Asp), TOPMed rs1196345944, gnomAD rs1196345944, REVEL 0.54, CADD 25.20, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- G17V (p.Gly17Val), TOPMed rs1196345944, gnomAD rs1196345944, REVEL 0.65, CADD 25.20
- G17S (p.Gly17Ser), gnomAD 7-143316261-G-A, REVEL 0.45, CADD 25.90
- S18* (p.Ser18Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- S18G (p.Ser18Gly), Ensembl rs1586479385, REVEL 0.17, CADD 16.30
- S18I (p.Ser18Ile), rs774525961, ClinGen CA4536807, ClinVar RCV003052596, ClinVar RCV003358064, REVEL 0.43, CADD 22.50, Uncertain significance, not specified; Inborn genetic diseases; Congenital myotonia, autosomal recessive
- S18N (p.Ser18Asn), ExAC rs774525961, TOPMed rs774525961, gnomAD rs774525961, REVEL 0.17, CADD 21.60, Uncertain significance
- S18R (p.Ser18Arg), ExAC rs748447969, gnomAD rs748447969
- S18T (p.Ser18Thr), rs1802289255, gnomAD 7-143316261-GGTAG, CADD 28.00
- D19E (p.Asp19Glu), rs886062031, TOPMed rs886062031, gnomAD rs886062031, ClinGen CA10623343, REVEL 0.24, CADD 19.30, Uncertain significance, Batten-Turner congenital myopathy
- D19Y (p.Asp19Tyr), gnomAD 7-143316267-G-T, REVEL 0.28, CADD 23.40
- P20A (p.Pro20Ala), ExAC rs772152846, TOPMed rs772152846, gnomAD rs772152846
- P20H (p.Pro20His), NCI-TCGA Cosmic COSV5836, Variant assessed as somatic; moderate impact.
- P20R (p.Pro20Arg), ExAC rs773346609, gnomAD rs773346609, REVEL 0.43, CADD 24.90
- P20T (p.Pro20Thr), ExAC rs772152846, TOPMed rs772152846, gnomAD rs772152846, REVEL 0.44, CADD 24.30, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- P20P (p.Pro20Pro), rs1369497283, gnomAD 7-143316272-C-T, CADD 10.80
- Q21S (p.Gln21Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- Q21R (p.Gln21Arg), gnomAD 7-143316274-A-G, REVEL 0.43, CADD 25.00
- Y22Y (p.Tyr22Tyr), gnomAD 7-143316278-C-T, CADD 8.53
- Y22* (p.Tyr22Ter), gnomAD 7-143316278-C-G, CADD 36.00
- Q23* (p.Gln23Ter), NCI-TCGA Cosmic COSV5836, NCI-TCGA Cosmic COSV5837, Variant assessed as somatic; high impact.
- Q23H (p.Gln23His), rs760729130, ExAC rs760729130, TOPMed rs760729130, gnomAD rs760729130, REVEL 0.33, CADD 23.40, Uncertain significance, Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal do
- Q23K (p.Gln23Lys), gnomAD 7-143316279-C-A, REVEL 0.39, CADD 19.40
- Q23Q (p.Gln23Gln), rs760729130, gnomAD 7-143316281-G-A, CADD 7.81
- Y24H (p.Tyr24His), TOPMed rs1802290055
- Y24* (p.Tyr24Ter), gnomAD 7-143316284-T-G, CADD 33.00
- Y24Y (p.Tyr24Tyr), gnomAD 7-143316284-T-C, CADD 4.76
- M25T (p.Met25Thr), ExAC rs766386297, gnomAD rs766386297, REVEL 0.16, CADD 22.80
- M25V (p.Met25Val), gnomAD rs1300860950, REVEL 0.14, CADD 5.59
- M25I (p.Met25Ile), gnomAD 7-143316287-G-T, REVEL 0.13, CADD 19.40
- P26L (p.Pro26Leu), NCI-TCGA Cosmic COSV1005, Variant assessed as somatic; moderate impact.
- P26S (p.Pro26Ser), rs775412383, NCI-TCGA Cosmic COSV1005, ExAC rs775412383, REVEL 0.17, CADD 14.40, Variant assessed as somatic; moderate impact.
- P26T (p.Pro26Thr), rs775412383, NCI-TCGA Cosmic COSV1005, ExAC rs775412383, REVEL 0.45, CADD 15.30, Variant assessed as somatic; moderate impact.
- F27L (p.Phe27Leu), rs2487015521, ClinGen CA369676916, ClinVar RCV003025867, REVEL 0.41, CADD 23.90, Uncertain significance, Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal do
- F27F (p.Phe27Phe), gnomAD 7-143316293-T-C, CADD 5.16
- E28* (p.Glu28Ter), ExAC rs762761541, gnomAD rs762761541
- E28Q (p.Glu28Gln), gnomAD 7-143316294-G-C, REVEL 0.40, CADD 25.40
- E28E (p.Glu28Glu), gnomAD 7-143316296-A-G, CADD 5.83
- H29P (p.His29Pro), rs146160029, ClinGen CA4536816, ClinVar RCV000361953, ClinVar RCV000442751, REVEL 0.81, CADD 24.70, Conflicting interpretations, not provided; Congenital myotonia, autosomal recessive form; Congenital myotonia
- C30F (p.Cys30Phe), TOPMed rs1802290576
- C30R (p.Cys30Arg), ExAC rs751290706, gnomAD rs751290706, REVEL 0.73, CADD 22.20
- C30C (p.Cys30Cys), gnomAD 7-143316302-C-T, CADD 7.83
- T31A (p.Thr31Ala), rs756977743, ClinGen CA4536818, ClinVar RCV001909991, ExAC rs756977743, REVEL 0.38, CADD 24.20, Uncertain significance, Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal do
- T31I (p.Thr31Ile), ExAC rs767076900, TOPMed rs767076900, gnomAD rs767076900, REVEL 0.50, CADD 24.40
- T31N (p.Thr31Asn), ExAC rs767076900, TOPMed rs767076900, gnomAD rs767076900, REVEL 0.40, CADD 23.90
- T31S (p.Thr31Ser), gnomAD 7-143316304-C-G, REVEL 0.42, CADD 22.80
- T31T (p.Thr31Thr), gnomAD 7-143316305-C-T, CADD 11.00
- Y33* (p.Tyr33Ter), rs138922145, ClinGen CA369677082, ClinVar RCV001381379, ESP rs138922145, Pathogenic
- Y33Y (p.Tyr33Tyr), rs138922145, gnomAD 7-143316311-C-T, CADD 0.93
- G34R (p.Gly34Arg), rs200889399, ClinGen CA4536821, ClinVar RCV000638254, ClinVar RCV004777788, REVEL 0.53, CADD 26.70, Uncertain significance, Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal do
- G34* (p.Gly34Ter), gnomAD 7-143316312-G-T, CADD 37.00
- L35P (p.Leu35Pro), ExAC rs779667702, gnomAD rs779667702
- P36L (p.Pro36Leu), rs2487015718, ClinGen CA369677129, ClinVar RCV003039003, REVEL 0.62, CADD 25.00, Uncertain significance, Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal do
- P36P (p.Pro36Pro), rs749833088, gnomAD 7-143316320-C-T, CADD 8.60
- S37F (p.Ser37Phe), gnomAD 7-143316322-C-T, REVEL 0.40, CADD 18.30
- S37S (p.Ser37Ser), gnomAD 7-143316323-T-C, CADD 1.21
- E38D (p.Glu38Asp), gnomAD rs1347626545, REVEL 0.26, CADD 23.40
- N39K (p.Asn39Lys), rs755414284, ClinGen CA4536824, ClinVar RCV004444232, ExAC rs755414284, REVEL 0.23, CADD 0.03, Uncertain significance, Inborn genetic diseases
- N39Y (p.Asn39Tyr), gnomAD rs1220204810, REVEL 0.22, CADD 23.10
- N39D (p.Asn39Asp), gnomAD 7-143316327-A-G, REVEL 0.14, CADD 19.40
- G40R (p.Gly40Arg), NCI-TCGA Cosmic COSV5837, Variant assessed as somatic; moderate impact.
- G40G (p.Gly40Gly), rs200344297, gnomAD 7-143316332-G-C, CADD 7.89
- G41D (p.Gly41Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G41S (p.Gly41Ser), gnomAD rs1471953068, REVEL 0.14, CADD 17.50
- G41V (p.Gly41Val), gnomAD rs1165421867, REVEL 0.13, CADD 17.70
- G41G (p.Gly41Gly), rs1351485530, gnomAD 7-143316335-C-T, CADD 8.01
- L42P (p.Leu42Pro), gnomAD 7-143316337-T-C, REVEL 0.20, CADD 15.60
- Q43* (p.Gln43Ter), rs563275093, ClinGen CA4536826, ClinVar RCV003805267, ClinVar RCV005409963, CADD 35.00, Pathogenic, in MCAR
- Q43H (p.Gln43His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact., in MCAR
- Q43L (p.Gln43Leu), NCI-TCGA Cosmic COSV1005, Variant assessed as somatic; moderate impact., in MCAR
- Q43P (p.Gln43Pro), rs868831424, ClinGen CA168249802, ClinVar RCV001039045, ClinVar RCV002551437, REVEL 0.44, CADD 23.20, Uncertain significance, Inborn genetic diseases; Congenital myotonia, autosomal dominant form; Congenita
- Q43R (p.Gln43Arg), rs868831424, UniProt VAR 075588, gnomAD rs868831424, REVEL 0.48, CADD 21.10, Likely pathogenic, not provided
- H44Q (p.His44Gln), NCI-TCGA Cosmic COSV5837, Variant assessed as somatic; high impact.
- R45G (p.Arg45Gly), rs371715660, ClinGen CA4536827, ClinVar RCV000560556, 1000Genomes rs371715660, REVEL 0.29, CADD 17.10, Uncertain significance, Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal do
- R45M (p.Arg45Met), NCI-TCGA Cosmic COSV5836, Variant assessed as somatic; moderate impact.
- R45S (p.Arg45Ser), TOPMed rs1802291784, gnomAD rs1802291784, REVEL 0.55, CADD 22.30, Likely benign
- L46P (p.Leu46Pro), Ensembl rs1802291843, REVEL 0.17, CADD 13.80
- L46S (p.Leu46Ser), gnomAD 7-143316347-GC-G, CADD 24.80
- R47Q (p.Arg47Gln), rs747166328, ClinGen CA4536829, ClinVar RCV002962314, ClinVar RCV003146697, REVEL 0.18, CADD 12.30, Uncertain significance, Inborn genetic diseases; Congenital myotonia, autosomal recessive form; Congenit
- R47W (p.Arg47Trp), rs185031797, ClinGen CA4536828, ClinVar RCV000638251, ClinVar RCV000714895, REVEL 0.20, CADD 21.30, Conflicting interpretations, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- R47R (p.Arg47Arg), gnomAD 7-143316353-G-A, CADD 5.16
- K48K (p.Lys48Lys), rs560922211, gnomAD 7-143316356-G-A, CADD 6.57
- D49V (p.Asp49Val), ExAC rs776644621, gnomAD rs776644621, REVEL 0.51, CADD 21.30
- D49M (p.Asp49Met), gnomAD 7-143316355-AG-A, CADD 24.50
- D49D (p.Asp49Asp), rs1586479527, gnomAD 7-143316359-T-C, CADD 0.45
- A50G (p.Ala50Gly), rs763907395, ClinGen CA4536833, ClinVar RCV003796078, 1000Genomes rs763907395, REVEL 0.09, CADD 4.56, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- A50T (p.Ala50Thr), rs762996741, ClinGen CA4536832, ClinVar RCV002728154, ExAC rs762996741, REVEL 0.18, CADD 0.53, Uncertain significance, Inborn genetic diseases
- A50V (p.Ala50Val), gnomAD 7-143316361-C-T, REVEL 0.12, CADD 8.10
- A50A (p.Ala50Ala), gnomAD 7-143316362-A-G, CADD 1.04
- G51A (p.Gly51Ala), ExAC rs75643846, REVEL 0.14, CADD 12.60
- G51D (p.Gly51Asp), ExAC rs75643846
- G51S (p.Gly51Ser), rs1487169721, ClinGen CA369677502, ClinVar RCV003795874, TOPMed rs1487169721, REVEL 0.11, CADD 7.20, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- G51V (p.Gly51Val), gnomAD 7-143316364-G-T, REVEL 0.19, CADD 14.10
- G51G (p.Gly51Gly), rs1554433799, gnomAD 7-143316365-C-T, CADD 1.57
- P52A (p.Pro52Ala), rs1802292476, ClinGen CA369677525, ClinVar RCV001050855, TOPMed rs1802292476, REVEL 0.10, CADD 2.11, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- P52H (p.Pro52His), gnomAD rs1244607320, REVEL 0.06, CADD 7.16
- P52L (p.Pro52Leu), gnomAD rs1244607320, REVEL 0.09, CADD 7.63
- P52S (p.Pro52Ser), NCI-TCGA Cosmic COSV1005, Variant assessed as somatic; moderate impact.
- P52T (p.Pro52Thr), TOPMed rs1802292476, Uncertain significance
- P52P (p.Pro52Pro), rs886062032, gnomAD 7-143316368-C-T, CADD 4.46
- R53C (p.Arg53Cys), rs767366093, ClinGen CA4536837, ClinVar RCV001158331, ClinVar RCV001195830, REVEL 0.38, CADD 13.60, Uncertain significance, not provided; Congenital myotonia, autosomal dominant form; Congenital myotonia
- R53G (p.Arg53Gly), ExAC rs767366093, TOPMed rs767366093, gnomAD rs767366093, REVEL 0.23, CADD 7.85, Uncertain significance
- R53H (p.Arg53His), rs750107386, NCI-TCGA Cosmic COSV5836, ExAC rs750107386, TOPMed rs750107386, REVEL 0.12, CADD 2.86, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- R53L (p.Arg53Leu), rs750107386, ClinGen CA369677573, ClinVar RCV003813442, ExAC rs750107386, REVEL 0.22, CADD 1.55, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- R53P (p.Arg53Pro), gnomAD 7-143316364-G-GCC, CADD 18.70
- R53A (p.Arg53Ala), gnomAD 7-143316364-GC-G, CADD 13.10
- H54N (p.His54Asn), gnomAD 7-143316372-C-A, REVEL 0.07, CADD 7.47
- H54Y (p.His54Tyr), gnomAD 7-143316372-C-T, REVEL 0.07, CADD 4.38
- H54R (p.His54Arg), gnomAD 7-143316373-A-G, REVEL 0.10, CADD 13.70
- H54H (p.His54His), rs755776577, gnomAD 7-143316374-C-T, CADD 5.21
- N55H (p.Asn55His), ExAC rs766032710, TOPMed rs766032710, gnomAD rs766032710, REVEL 0.28, CADD 19.90, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- N55N (p.Asn55Asn), rs753251995, gnomAD 7-143316377-C-T, CADD 3.12
- N55K (p.Asn55Lys), gnomAD 7-143316377-C-G, REVEL 0.10, CADD 9.36
- V56F (p.Val56Phe), rs202120426, ClinGen CA369677640, ClinVar RCV003792202, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- V56I (p.Val56Ile), rs202120426, ClinGen CA4536842, NCI-TCGA Cosmic COSV5837, ClinVar RCV000711224, REVEL 0.14, CADD 1.45, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- H57R (p.His57Arg), gnomAD rs1415954354, REVEL 0.17, CADD 12.00
- P58A (p.Pro58Ala), ExAC rs779274886, TOPMed rs779274886, gnomAD rs779274886, REVEL 0.26, CADD 16.90, Uncertain significance, Inborn genetic diseases
- P58L (p.Pro58Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P58S (p.Pro58Ser), gnomAD 7-143316384-C-T, REVEL 0.32, CADD 18.80
- P58T (p.Pro58Thr), gnomAD 7-143316384-C-A, REVEL 0.36, CADD 18.70
- P58P (p.Pro58Pro), gnomAD 7-143316386-C-A, CADD 7.03
- T59A (p.Thr59Ala), TOPMed rs1364660030
- T59I (p.Thr59Ile), gnomAD 7-143316388-C-T, REVEL 0.25, CADD 21.10
- T59T (p.Thr59Thr), gnomAD 7-143316389-A-T, CADD 4.31
- Q60H (p.Gln60His), TOPMed rs1296103687, Uncertain significance, not provided
- Q60* (p.Gln60Ter), gnomAD 7-143316390-C-T, CADD 38.00
- I61L (p.Ile61Leu), rs2487025721, ClinGen CA369678861, ClinVar RCV002302104, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- G63C (p.Gly63Cys), ExAC rs781383745, gnomAD rs781383745, REVEL 0.69, CADD 26.20, Uncertain significance
- G63S (p.Gly63Ser), rs781383745, ClinGen CA369678914, ClinVar RCV003782205, ExAC rs781383745, REVEL 0.57, CADD 25.40, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- G63A (p.Gly63Ala), gnomAD 7-143319760-TG-T, CADD 28.20
- G63D (p.Gly63Asp), gnomAD 7-143319762-G-A, REVEL 0.61, CADD 25.30
- G63G (p.Gly63Gly), rs2116834513, gnomAD 7-143319763-C-A, CADD 7.65
- H65D (p.His65Asp), rs2487025762, ClinGen CA369678962, ClinVar RCV003801775, Uncertain significance, Congenital myotonia, autosomal dominant form; Congenital myotonia, autosomal rec
- H65R (p.His65Arg), rs1802376355, ClinGen CA369678968, ClinVar RCV003144997, TOPMed rs1802376355, REVEL 0.18, CADD 21.10, Uncertain significance, Inborn genetic diseases; not provided
- H65H (p.His65His), rs369579634, gnomAD 7-143319769-C-T, CADD 7.70
Public CLCN1 analysis runs
- CLCN1 analysis run — CLCN1 (1,686 variants) — completed 2026-08-18