NM_000083.3(CLCN1):c.950G>A (p.Arg317Gln) AND Congenital myotonia, autosomal dominant form

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Feb 7, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000019095.31

Allele description [Variation Report for NM_000083.3(CLCN1):c.950G>A (p.Arg317Gln)]

NM_000083.3(CLCN1):c.950G>A (p.Arg317Gln)

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.950G>A (p.Arg317Gln)

HGVS:

NC_000007.14:g.143330868G>A
NG_009815.2:g.19743G>A
NM_000083.3:c.950G>AMANE SELECT
NP_000074.3:p.Arg317Gln
NC_000007.13:g.143027961G>A
NG_009815.1:g.19743G>A
NM_000083.2:c.950G>A
NR_046453.2:n.1055G>A
P35523:p.Arg317Gln

Protein change:

R317Q; ARG317GLN

Links:

UniProtKB: P35523#VAR_001600; OMIM: 118425.0011; dbSNP: rs80356702

NCBI 1000 Genomes Browser:

rs80356702

Molecular consequence:

NM_000083.3:c.950G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_046453.2:n.1055G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000039383	OMIM	no assertion criteria provided	Pathogenic (Mar 1, 1998)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 8533761, 10737121
SCV001190886	HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - AGHI WGS	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 26, 2019)	maternal	research	PubMed (1) [See all records that cite this PMID]
SCV002549792	Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences	no assertion criteria provided	Pathogenic (Apr 6, 2022)	germline	research
SCV005049859	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 7, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	maternal	yes	1	not provided	not provided	1	not provided	research
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

Identification of two mutations and a polymorphism in the chloride channel CLCN-1 in patients with Becker's generalized myotonia.

Esteban J, Neumeyer AM, McKenna-Yasek D, Brown RH.

Neurogenetics. 1998 Mar;1(3):185-8.

PubMed [citation]

PMID:: 10737121

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000039383.2

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

Description

The arg317-to-gln (R317Q) mutation illustrates the resultant occurrence of either autosomal dominant myotonia congenita (160800) or autosomal recessive myotonia congenita (255700), depending on the family background. Meyer-Kleine et al. (1995) observed the R317Q mutation in dominant Thomsen myotonia congenita; Esteban et al. (1998) observed it in Becker myotonia congenita and pointed to other mutations that had been observed as a recessive or a dominant, depending on the particular family.

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

From HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - AGHI WGS, SCV001190886.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	PubMed (1)

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

From Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, SCV002549792.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	not provided

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

From Baylor Genetics, SCV005049859.1

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

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

Last Updated: Sep 29, 2024

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