NM_000083.3(CLCN1):c.568_569delinsTC (p.Gly190Ser) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Oct 15, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000530150.6

Allele description [Variation Report for NM_000083.3(CLCN1):c.568_569delinsTC (p.Gly190Ser)]

NM_000083.3(CLCN1):c.568_569delinsTC (p.Gly190Ser)

Gene:
CLCN1:chloride voltage-gated channel 1 [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
7q34
Genomic location:
Preferred name:
NM_000083.3(CLCN1):c.568_569delinsTC (p.Gly190Ser)
HGVS:
  • NC_000007.14:g.143321720_143321721delinsTC
  • NG_009815.1:g.10595_10596delinsTC
  • NG_009815.2:g.10595_10596delinsTC
  • NM_000083.3:c.568_569delinsTCMANE SELECT
  • NP_000074.3:p.Gly190Ser
  • NC_000007.13:g.143018813_143018814delinsTC
  • NM_000083.2:c.568_569delGGinsTC
  • NR_046453.2:n.670_671delinsTC
  • p.GLY190SER
Protein change:
G190S
Links:
dbSNP: rs797045032
NCBI 1000 Genomes Browser:
rs797045032
Molecular consequence:
  • NM_000083.3:c.568_569delinsTC - missense variant - [Sequence Ontology: SO:0001583]
  • NR_046453.2:n.670_671delinsTC - 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
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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000649786Invitaecriteria provided, single submitter
Pathogenic
(Oct 15, 2020)
germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A large cohort of myotonia congenita probands: novel mutations and a high-frequency mutation region in exons 4 and 5 of the CLCN1 gene.

Brugnoni R, Kapetis D, Imbrici P, Pessia M, Canioni E, Colleoni L, de Rosbo NK, Morandi L, Cudia P, Gashemi N, Bernasconi P, Desaphy JF, Conte D, Mantegazza R.

J Hum Genet. 2013 Sep;58(9):581-7. doi: 10.1038/jhg.2013.58. Epub 2013 Jun 6.

PubMed [citation]
PMID:
23739125

Low-rate repetitive nerve stimulation protocol in an Italian cohort of patients affected by recessive myotonia congenita.

Modoni A, D'Amico A, Dallapiccola B, Mereu ML, Merlini L, Pagliarani S, Pisaneschi E, Silvestri G, Torrente I, Valente EM, Lo Monaco M.

J Clin Neurophysiol. 2011 Feb;28(1):39-44. doi: 10.1097/WNP.0b013e31820510d7.

PubMed [citation]
PMID:
21221019
See all PubMed Citations (9)

Details of each submission

From Invitae, SCV000649786.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

This sequence change replaces glycine with serine at codon 190 of the CLCN1 protein (p.Gly190Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the heterozygous, homozygous and compound heterozygous state in many individuals affected myotonia congenita (PMID: 19697366, 22921319, 22521272, 23739125, 21221019, 24349310, 26007199). It has been shown to co-segregate with disease in two families; in the heterozygous state this variant was reported to be incompletely penetrant and in the homozygous state it was reported to cause a more severe phenotype (PMID: 19697366, 22921319). ClinVar contains an entry for this variant (Variation ID: 209139). Experimental studies have shown that this missense change alters the voltage-dependent activation kinetics of the CLCN1 channel (PMID: 22521272, 23933576). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 18, 2021

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