ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.382A>G (p.Met128Val) (rs80356699)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001049292 SCV001213337 likely pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2019-04-25 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 128 of the CLCN1 protein (p.Met128Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with myotonia congenita in a family (PMID: 12661046, 14639587). ClinVar contains an entry for this variant (Variation ID: 17546). This variant has been reported to affect CLCN1 protein function (PMID: 14639587). This variant disrupts the p.Met128 amino acid residue in CLCN1. Other variant(s) that disrupt this residue have been observed in individuals with CLCN1-related conditions (PMID: 19949657, 23113340, 24625573), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000019100 SCV000039388 pathogenic Congenital myotonia, autosomal dominant form 2003-04-01 no assertion criteria provided literature only
GeneReviews RCV000020109 SCV000040429 pathologic Myotonia congenita 2011-04-12 no assertion criteria provided curation Converted during submission to Pathogenic.

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