ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.1892C>T (p.Thr631Ile)

gnomAD frequency: 0.00002  dbSNP: rs749762818
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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 RCV000794383 SCV000933788 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2022-10-03 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 631 of the CLCN1 protein (p.Thr631Ile). This variant is present in population databases (rs749762818, gnomAD 0.04%). This missense change has been observed in individual(s) with a family affected with myotonia congenita this variant was reported in unaffected individuals and not in affected individuals, indicating that it is not the cause of disease in this family (PMID: 16629771). ClinVar contains an entry for this variant (Variation ID: 641198). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Experimental studies have shown that this missense change does not substantially affect CLCN1 function (PMID: 17097617, 18035046). 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.
Illumina Laboratory Services, Illumina RCV001163173 SCV001325184 likely benign Batten-Turner congenital myopathy 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

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