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

Germline classification:: Pathogenic/Likely pathogenic (3 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:: RCV000019094.31

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 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000039382	OMIM	no assertion criteria provided	Pathogenic (Mar 1, 1998)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 8533761, 10737121
SCV001369057	Centre for Mendelian Genomics, University Medical Centre Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 1, 2016)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005049691	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]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000039382

OMIM

no assertion criteria provided

Pathogenic
(Mar 1, 1998)

germline

literature only

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

SCV001369057

Centre for Mendelian Genomics, University Medical Centre Ljubljana

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 1, 2016)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV005049691

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	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
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, SCV000039382.2

#	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 Centre for Mendelian Genomics, University Medical Centre Ljubljana, SCV001369057.2

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

Description

This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PP3,PP2.

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

From Baylor Genetics, SCV005049691.1

#	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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