ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.209C>T (p.Ser70Leu)

gnomAD frequency: 0.00001  dbSNP: rs769312894
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001974802 SCV002210858 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2021-03-16 criteria provided, single submitter clinical testing 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. 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 not expected to disrupt CLCN1 protein function. This variant has been observed in individual(s) with autosomal recessive myotonia congenita (PMID: 26502825). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs769312894, ExAC 0.004%). This sequence change replaces serine with leucine at codon 70 of the CLCN1 protein (p.Ser70Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine.
Athena Diagnostics RCV004999560 SCV005620674 uncertain significance not provided 2024-10-24 criteria provided, single submitter clinical testing Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity. (http://gnomad.broadinstitute.org) This variant has been identified in at least one individual with clinical features associated with this gene. Assessment of experimental evidence regarding the effect of this variant on protein function is inconclusive. (PMID: 34529042, 34529042)

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