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NM_000083.3(CLCN1):c.1453A>G (p.Met485Val) AND Batten-Turner congenital myopathy

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 18, 2018
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:
RCV000778823.6

Allele description [Variation Report for NM_000083.3(CLCN1):c.1453A>G (p.Met485Val)]

NM_000083.3(CLCN1):c.1453A>G (p.Met485Val)

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.1453A>G (p.Met485Val)
HGVS:
  • NC_000007.14:g.143339304A>G
  • NG_009815.2:g.28179A>G
  • NM_000083.3:c.1453A>GMANE SELECT
  • NP_000074.3:p.Met485Val
  • NC_000007.13:g.143036397A>G
  • NG_009815.1:g.28179A>G
  • NM_000083.2:c.1453A>G
  • NR_046453.2:n.1408A>G
  • P35523:p.Met485Val
Protein change:
M485V
Links:
UniProtKB: P35523#VAR_001609; dbSNP: rs146457619
NCBI 1000 Genomes Browser:
rs146457619
Molecular consequence:
  • NM_000083.3:c.1453A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_046453.2:n.1408A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Batten-Turner congenital myopathy
Identifiers:
MONDO: MONDO:0100468; MedGen: C0027127; OMIM: 255300

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000915214Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)		Pathogenic
(Dec 18, 2018) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

CLCN1 mutations in Czech patients with myotonia congenita, in silico analysis of novel and known mutations in the human dimeric skeletal muscle chloride channel.

Skálová D, Zídková J, Voháňka S, Mazanec R, Mušová Z, Vondráček P, Mrázová L, Kraus J, Réblová K, Fajkusová L.

PLoS One. 2013;8(12):e82549. doi: 10.1371/journal.pone.0082549.

PubMed [citation]
PMID:
24349310
PMCID:
PMC3859631

Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia.

Meyer-Kleine C, Steinmeyer K, Ricker K, Jentsch TJ, Koch MC.

Am J Hum Genet. 1995 Dec;57(6):1325-34.

PubMed [citation]
PMID:
8533761
PMCID:
PMC1801423
See all PubMed Citations (7)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000915214.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

The CLCN1 c.1453A>G (p.Met485Val) missense variant has been reported in at least six studies in which it is found in a total of 13 individuals with myotonia congenita, including two in a homozygous state, ten in a compound heterozygous state (including two siblings) and one proband with unspecified zygosity (Meyer-Kleine et al. 1995; Fialho et al. 2007; Mazon et al. 2012; Skálová et al. 2013; Brugnoni et al. 2013; Hoche et al. 2014). The variant has also been reported in a heterozygous state in at least three unaffected relatives (Meyer-Kleine et al. 1995; Hoche et al. 2014). The p.Met485Val variant was absent from 200 control alleles but is reported at a frequency of 0.000773 in the Other population of the Genome Aggregation Database. Functional studies involving expression in Xenopus oocytes demonstrated that the variant led to a drastic reduction of the single channel conductance compared to wildtype (Wollnik et al. 1997). Based on the evidence, the p.Met485Val variant is classified as pathogenic for myotonia congenita. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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

Last Updated: Nov 10, 2024