ClinVar Miner

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

dbSNP: rs80356699
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001049292 SCV001213337 likely pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2021-09-29 criteria provided, single submitter clinical testing 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. 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. Experimental studies have shown that this missense change affects CLCN1 function (PMID: 14639587). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 17546). This missense change has been observed in individual(s) with autosomal dominant myotonia congenita (PMID: 12661046, 14639587). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). 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.
OMIM RCV000019100 SCV000039388 pathogenic Congenital myotonia, autosomal dominant form 2003-04-01 no assertion criteria provided literature only
GeneReviews RCV000020109 SCV000040429 not provided Batten-Turner congenital myopathy no assertion provided literature only

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