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:: RCV001209375.10

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

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:: BECKER DISEASE; Becker Generalized Myotonia
Identifiers:: MONDO: MONDO:0009715; MedGen: C0751360; Orphanet: 614; OMIM: 255700

Name:: Congenital myotonia, autosomal dominant form (THD)
Synonyms:: THOMSEN DISEASE; Myotonia congenita autosomal dominant
Identifiers:: MONDO: MONDO:0008055; MedGen: C2936781; Orphanet: 614; OMIM: 160800

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001380807	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 22, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34529042, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001380807

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 22, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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, SCV001380807.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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. ClinVar contains an entry for this variant (Variation ID: 939897). 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).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 23, 2026

ClinVar

Relating variation to medicine