ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.817G>A (p.Val273Met)

gnomAD frequency: 0.00001  dbSNP: rs921162119
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000821657 SCV000962426 pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2023-12-09 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 273 of the CLCN1 protein (p.Val273Met). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individuals with autosomal recessive myotonia congenita (PMID: 27614575, 32117024, 34529042). It has also been observed to segregate with disease in related individuals. This variant has been reported in individual(s) with autosomal dominant myotonia congenita (PMID: 32117024); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 663722). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CLCN1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV001091921 SCV001248203 pathogenic not provided 2018-06-01 criteria provided, single submitter clinical testing

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