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NM_000083.3(CLCN1):c.1453A>G (p.Met485Val) AND CLCN1-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 6, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV004737396.1

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:
CLCN1-related disorder
Synonyms:
CLCN1-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005362908PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Pathogenic
(May 6, 2024) 		germlineclinical testing

Help

Summary from all submissions

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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV005362908.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The CLCN1 c.1453A>G variant is predicted to result in the amino acid substitution p.Met485Val. This variant has been reported in the homozygous and compound heterozgyous states in mutliple individuals with autosomal recessive myotonia congenita (Dupré et al. 2009. PubMed ID: 18337100; Mazón et al. 2012. PubMed ID: 22094069; Milla et al. 2019. PubMed ID: 31544778; Suetterlin et al. 2022. PubMed ID: 34529042) and has been observed to co-segregate with disease in at least one family (Meyer-Kleine et al. 1995. PubMed ID: 8533761). In vitro functional studies have demonstrated that this variant negatively impacts chloride channel function (Wollnik et al. 1997. PubMed ID: 9158157; Kubisch et al. 1998. PubMed ID: 9736777; Tan et al. 2013. PubMed ID: 24037712; Suetterlin et al. 2022. PubMed ID: 34529042). This variant is reported in 0.065% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Of note, other missense variants at this amino acid residue (p.Met485Lys, p.Met485Glu) have been reported in individuals with CLCN1-related disease (Fialho et al. 2007. PubMed ID: 17932099; Suetterlin et al. 2022. PubMed ID: 34529042). Taken together, this variant is interpreted as pathogenic for autosomal recessive CLCN1-related disorders.

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

Last Updated: Nov 10, 2024