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NM_000083.3(CLCN1):c.1679T>C (p.Met560Thr) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 2, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001203792.8

Allele description [Variation Report for NM_000083.3(CLCN1):c.1679T>C (p.Met560Thr)]

NM_000083.3(CLCN1):c.1679T>C (p.Met560Thr)

Gene:
CLCN1:chloride voltage-gated channel 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q34
Genomic location:
Preferred name:
NM_000083.3(CLCN1):c.1679T>C (p.Met560Thr)
HGVS:
  • NC_000007.14:g.143342025T>C
  • NG_009815.2:g.30900T>C
  • NM_000083.3:c.1679T>CMANE SELECT
  • NP_000074.3:p.Met560Thr
  • NC_000007.13:g.143039118T>C
  • NG_009815.1:g.30900T>C
  • NM_000083.2:c.1679T>C
  • NR_046453.2:n.1634T>C
Protein change:
M560T
Links:
dbSNP: rs1269268607
NCBI 1000 Genomes Browser:
rs1269268607
Molecular consequence:
  • NM_000083.3:c.1679T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_046453.2:n.1634T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Congenital myotonia, autosomal recessive form
Synonyms:
Myotonia congenita autosomal recessive; Becker disease; Myotonia generalized; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009715; MedGen: C0751360; Orphanet: 614; OMIM: 255700
Name:
Congenital myotonia, autosomal dominant form (THD)
Synonyms:
Myotonia congenita autosomal dominant; Thomsen disease; Thomsen's disease
Identifiers:
MONDO: MONDO:0008055; MedGen: C2936781; Orphanet: 614; OMIM: 160800

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001374969Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Dec 2, 2023)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Novel chloride channel gene mutations in two unrelated Chinese families with myotonia congenita.

Gao F, Ma FC, Yuan ZF, Yang CW, Li HF, Xia ZZ, Shui QX, Jiang KW.

Neurol India. 2010 Sep-Oct;58(5):743-6. doi: 10.4103/0028-3886.72163.

PubMed [citation]
PMID:
21045501

[Compound heterozygous mutations in the muscle chloride channel gene (CLCN1) in a Japanese family with Thomsen's disease].

Sasaki R, Takahashi MP, Kokunai Y, Hirayama M, Ibi T, Tomimoto H, Mochizuki H, Sahashi K.

Rinsho Shinkeigaku. 2013;53(4):316-9. Japanese.

PubMed [citation]
PMID:
23603549
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001374969.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 560 of the CLCN1 protein (p.Met560Thr). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with myotonia congenita (PMID: 21045501, 23603549, 24349310, 25749817, 26260254). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 935242). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CLCN1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024