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NM_000083.3(CLCN1):c.1190T>A (p.Val397Asp) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 22, 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:
RCV001209375.8

Allele description [Variation Report for NM_000083.3(CLCN1):c.1190T>A (p.Val397Asp)]

NM_000083.3(CLCN1):c.1190T>A (p.Val397Asp)

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.1190T>A (p.Val397Asp)
HGVS:
  • NC_000007.14:g.143332442T>A
  • NG_009815.2:g.21317T>A
  • NM_000083.3:c.1190T>AMANE SELECT
  • NP_000074.3:p.Val397Asp
  • NC_000007.13:g.143029535T>A
  • NG_009815.1:g.21317T>A
  • NM_000083.2:c.1190T>A
  • NR_046453.2:n.1295T>A
Protein change:
V397D
Links:
dbSNP: rs368958317
NCBI 1000 Genomes Browser:
rs368958317
Molecular consequence:
  • NM_000083.3:c.1190T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_046453.2:n.1295T>A - 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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001380807Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 22, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Translating genetic and functional data into clinical practice: a series of 223 families with myotonia.

Suetterlin K, Matthews E, Sud R, McCall S, Fialho D, Burge J, Jayaseelan D, Haworth A, Sweeney MG, Kullmann DM, Schorge S, Hanna MG, Männikkö R.

Brain. 2022 Apr 18;145(2):607-620. doi: 10.1093/brain/awab344.

PubMed [citation]
PMID:
34529042
PMCID:
PMC9014745

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001380807.5

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

Description

This missense change has been observed in individual(s) with clinical features of CLCN1-related conditions (PMID: 34529042). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 397 of the CLCN1 protein (p.Val397Asp). ClinVar contains an entry for this variant (Variation ID: 939897). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects CLCN1 function (PMID: 34529042). 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.

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

Last Updated: Sep 29, 2024