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NM_000083.3(CLCN1):c.1261dup (p.Arg421fs) AND Congenital myotonia, autosomal recessive form

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 24, 2019
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:
RCV001193451.1

Allele description [Variation Report for NM_000083.3(CLCN1):c.1261dup (p.Arg421fs)]

NM_000083.3(CLCN1):c.1261dup (p.Arg421fs)

Gene:
CLCN1:chloride voltage-gated channel 1 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
7q34
Genomic location:
Preferred name:
NM_000083.3(CLCN1):c.1261dup (p.Arg421fs)
HGVS:
  • NC_000007.14:g.143332733dup
  • NG_009815.1:g.21608dup
  • NM_000083.3:c.1261dupMANE SELECT
  • NP_000074.3:p.Arg421fs
  • NC_000007.13:g.143029822_143029823insC
  • NC_000007.13:g.143029826dup
  • NM_000083.2:c.1261dup
  • NM_000083.2:c.1261dupC
  • p.Arg421Profs*9
Protein change:
R421fs
Links:
dbSNP: rs763633152
NCBI 1000 Genomes Browser:
rs763633152
Molecular consequence:
  • NM_000083.3:c.1261dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001362283Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(May 24, 2019) 		germlineclinical testing

PubMed (2)
[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

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

Prevalence and mutation spectrum of skeletal muscle channelopathies in the Netherlands.

Stunnenberg BC, Raaphorst J, Deenen JCW, Links TP, Wilde AA, Verbove DJ, Kamsteeg EJ, van den Wijngaard A, Faber CG, van der Wilt GJ, van Engelen BGM, Drost G, Ginjaar HB.

Neuromuscul Disord. 2018 May;28(5):402-407. doi: 10.1016/j.nmd.2018.03.006. Epub 2018 Mar 9.

PubMed [citation]
PMID:
29606556

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001362283.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: CLCN1 c.1261dupC (p.Arg421ProfsX9) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2.8e-05 in 251658 control chromosomes (gnomAD) and has been reported in the literature in individuals affected with Congenital and generalized myotonia in an autosomal recessive form (Meyer-Kleine_1995, Stunnenberg_2018). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Sep 29, 2024