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NM_000083.3(CLCN1):c.979+1G>A AND Congenital myotonia, autosomal recessive form

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 1, 1994
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000019086.23

Allele description [Variation Report for NM_000083.3(CLCN1):c.979+1G>A]

NM_000083.3(CLCN1):c.979+1G>A

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.979+1G>A
HGVS:
  • NC_000007.14:g.143330898G>A
  • NG_009815.2:g.19773G>A
  • NM_000083.3:c.979+1G>AMANE SELECT
  • NC_000007.13:g.143027991G>A
  • NM_000083.2:c.979+1G>A
Note:
ClinGen staff contributed the HGVS expression for this variant.
Nucleotide change:
IVSDS, G-A, +1
Links:
OMIM: 118425.0003; dbSNP: rs1563078827
NCBI 1000 Genomes Browser:
rs1563078827
Molecular consequence:
  • NM_000083.3:c.979+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000039374OMIM
no assertion criteria provided
Pathogenic
(Jun 1, 1994)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Genomic organization of the human muscle chloride channel CIC-1 and analysis of novel mutations leading to Becker-type myotonia.

Lorenz C, Meyer-Kleine C, Steinmeyer K, Koch MC, Jentsch TJ.

Hum Mol Genet. 1994 Jun;3(6):941-6.

PubMed [citation]
PMID:
7951242

Details of each submission

From OMIM, SCV000039374.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In affected members of a German family with recessive myotonia (255700), Lorenz et al. (1994) identified compound heterozygosity for 2 mutations in the CLCN1 gene: a 979G-A transition in a splice consensus site at the end of exon 8, and a 1488G-T transversion in exon 14, resulting in an arg496-to-ser (R496S; 118425.0004). Functional expression of R496S cRNA in Xenopus oocytes yielded no detectable currents. Furthermore, it did not suppress wildtype currents in coexpression assay, confirming it as a recessive mutation. The G-to-A transition in exon 8 was stated to affect the last nucleotide of the exon. If this interfered with mRNA splicing at that exon/intron boundary, the translation product would be terminated by a stop codon after 51 additional amino acids or other splice sites in the intron might be used. Alternatively, if splicing were normal, this mutation would lead to a substitution of isoleucine for valine at position 327 (V327I). Since this residue is not conserved among the members of this gene family and most members have negatively charged glutamate residues at this position, it is unlikely that such a substitution would have a dramatic effect on channel function. This would argue for an aberrant splicing as the effect of the G979A mutation.

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

Last Updated: Jun 10, 2023