ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.2647C>A (p.Pro883Thr)

gnomAD frequency: 0.00002  dbSNP: rs764347321
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001213417 SCV001385046 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2023-11-28 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 883 of the CLCN1 protein (p.Pro883Thr). This variant is present in population databases (rs764347321, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of myotonia congenita (PMID: 17932099, 29935101, 34529042). ClinVar contains an entry for this variant (Variation ID: 943263). 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. Experimental studies have shown that this missense change affects CLCN1 function (PMID: 29935101, 34529042). 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.

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