ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.2495C>T (p.Thr832Ile)

dbSNP: rs755343536
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001257255 SCV001433797 pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2023-01-23 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 978544). This missense change has been observed in individual(s) with autosomal recessive myotonia congenita (PMID: 29935101; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs755343536, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 832 of the CLCN1 protein (p.Thr832Ile). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects CLCN1 function (PMID: 29935101). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CLCN1 protein function.

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