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NM_000083.3(CLCN1):c.2434C>T (p.Gln812Ter) AND Congenital myotonia, autosomal recessive form

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Feb 14, 2023
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:
RCV002290823.4

Allele description [Variation Report for NM_000083.3(CLCN1):c.2434C>T (p.Gln812Ter)]

NM_000083.3(CLCN1):c.2434C>T (p.Gln812Ter)

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.2434C>T (p.Gln812Ter)
HGVS:
  • NC_000007.14:g.143350402C>T
  • NG_009815.2:g.39277C>T
  • NM_000083.3:c.2434C>TMANE SELECT
  • NP_000074.3:p.Gln812Ter
  • NC_000007.13:g.143047495C>T
  • NG_009815.1:g.39277C>T
  • NM_000083.2:c.2434C>T
  • NR_046453.2:n.2389C>T
Protein change:
Q812*
Links:
dbSNP: rs772150974
NCBI 1000 Genomes Browser:
rs772150974
Molecular consequence:
  • NR_046453.2:n.2389C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000083.3:c.2434C>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002579613MGZ Medical Genetics Center
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Nov 22, 2021) 		germlineclinical testing

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

SCV004176373Neuberg Centre For Genomic Medicine, NCGM
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Feb 14, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From MGZ Medical Genetics Center, SCV002579613.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From Neuberg Centre For Genomic Medicine, NCGM, SCV004176373.1

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

Description

The stop gained c.2434C>T (p.Gln812Ter) variant in CLCN1 gene has been previously reported in homozygous and compound heterozygous states in multiple individuals affected with Myotonia congenita (Imbrici et al., 2015; Brugnoni et al., 2013; Modoni et al., 2011). The p.Gln812Ter variant has been reported with allele frequency of 0.002% in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic (multiple submissions). The nucleotide change c.2434C>T in CLCN1 gene is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This sequence change creates a premature translational stop signal (p.Gln812Ter) in the CLCN1 gene. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants in CLCN1 gene have been previously reported to be pathogenic (Brugnoni et al., 2013). For these reasons, this variant has been classified as Pathogenic

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

Last Updated: Sep 29, 2024