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NM_000083.3(CLCN1):c.2680C>T (p.Arg894Ter) AND Batten-Turner congenital myopathy

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
May 7, 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:
RCV000020107.10

Allele description [Variation Report for NM_000083.3(CLCN1):c.2680C>T (p.Arg894Ter)]

NM_000083.3(CLCN1):c.2680C>T (p.Arg894Ter)

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.2680C>T (p.Arg894Ter)
HGVS:
  • NC_000007.14:g.143351678C>T
  • NG_009815.2:g.40553C>T
  • NM_000083.3:c.2680C>TMANE SELECT
  • NP_000074.3:p.Arg894Ter
  • NC_000007.13:g.143048771C>T
  • NG_009815.1:g.40553C>T
  • NM_000083.2:c.2680C>T
  • NR_046453.2:n.2635C>T
  • p.Arg894*
  • p.Arg894X
Protein change:
R894*; ARG894TER
Links:
OMIM: 118425.0015; dbSNP: rs55960271
NCBI 1000 Genomes Browser:
rs55960271
Molecular consequence:
  • NR_046453.2:n.2635C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000083.3:c.2680C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000040427GeneReviews
no classification provided
not providedgermlineliterature only

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

SCV000467134Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)		Pathogenic
(May 7, 2018) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, literature only

Citations

PubMed

Myotonia and the muscle chloride channel: dominant mutations show variable penetrance and founder effect.

Koty PP, Pegoraro E, Hobson G, Marks HG, Turel A, Flagler D, Cadaldini M, Angelini C, Hoffman EP.

Neurology. 1996 Oct;47(4):963-8.

PubMed [citation]
PMID:
8857727

Novel muscle chloride channel mutations and their effects on heterozygous carriers.

Mailänder V, Heine R, Deymeer F, Lehmann-Horn F.

Am J Hum Genet. 1996 Feb;58(2):317-24.

PubMed [citation]
PMID:
8571958
PMCID:
PMC1914535
See all PubMed Citations (12)

Details of each submission

From GeneReviews, SCV000040427.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (7)

Description

Associated with autosomal recessive and autosomal dominant mode of inheritance

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

From Illumina Laboratory Services, Illumina, SCV000467134.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The CLCN1 c.2680C>T (p.Arg894Ter) variant is a stop-gained variant that is predicted to result in premature termination of the protein. The p.Arg894Ter variant is well-described in the literature as a common pathogenic variant (Dunø et al. 2015). Across a selection of five studies, the variant was detected in a homozygous state in nine individuals, in a compound heterozygous state in 32 individuals and in a heterozygous state in 12 individuals, all affected with myotonia congenita (Meyer-Kleine et al. 1995; Papponen et al. 1999; Sun et al. 2001; Suominen et al. 2008; Rayan et al. 2012). The variant was present in 1/324 control chromosomes and is reported at a frequency of 0.03 in the Finnish in Finland population of the 1000 Genomes Project. Functional studies in Xenopus oocytes demonstrated that the variant resulted in greatly reduced choride currents compared to wild type, to a level that was intermediate between the reductions seen for a known “fully dominant” pathogenic variant, and a known “fully recessive” pathogenic variant (Meyer-Kleine et al. 1995). Experiments in L6 myotubes and isolated rat myofibers indicated that the variant did not inhibit transport of the protein but did cause reduced stability (Papponen et al. 2008). Based on the collective evidence and the potential impact of stop-gained variants, the p.Arg894Ter variant is classified as pathogenic for the autosomal recessive form of 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: Oct 20, 2024