ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.1919T>G (p.Val640Gly)

dbSNP: rs1803111906
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001312155 SCV001502616 pathogenic not provided 2020-10-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001871788 SCV002287701 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2022-01-05 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 640 of the CLCN1 protein (p.Val640Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive myotonia congenita (PMID: 23739125, 26096614). ClinVar contains an entry for this variant (Variation ID: 1013568). 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. Experimental studies have shown that this missense change affects CLCN1 function (PMID: 26096614). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
MGZ Medical Genetics Center RCV002290687 SCV002580035 likely pathogenic Congenital myotonia, autosomal recessive form 2022-05-31 criteria provided, single submitter clinical testing

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