ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.1886T>C (p.Leu629Pro)

dbSNP: rs1009716258
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
DASA RCV001824196 SCV002073751 likely pathogenic Congenital myotonia, autosomal dominant form 2022-02-05 criteria provided, single submitter clinical testing The c.1886T>C;p.(Leu629Pro) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (PMID: 27582597) - PS4_supporting. This variant is not present in population databases (rs1009716258; gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. The p.(Leu629Pro) was detected in trans with a pathogenic variant (PMID: 27582597) - PM3_supporting. The variant co-segregated with disease in multiple affected family members (PMID: 27582597) - PP1. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001885370 SCV002197502 pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2022-08-31 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 1339487). This missense change has been observed in individuals with autosomal recessive myotonia congenita (PMID: 27582597; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 629 of the CLCN1 protein (p.Leu629Pro).
CeGaT Center for Human Genetics Tuebingen RCV002292668 SCV002586204 likely pathogenic not provided 2022-08-01 criteria provided, single submitter clinical testing CLCN1: PM2, PM3, PP1, PP3

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