ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.502C>G (p.Pro168Ala)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics, Royal Melbourne Hospital RCV003994671 SCV004812565 uncertain significance Congenital myotonia, autosomal recessive form 2024-03-01 criteria provided, single submitter clinical testing This sequence change in CLCN1 is predicted to replace proline with alanine at codon 168, p.(Pro168Ala). The proline residue is highly conserved (100 vertebrates, Multiz Alignments), and is located in the transmembrane alpha-helix C domain (PMID: 23739125, 34529042). There is a small physicochemical difference between proline and alanine. This variant is absent from the population database gnomAD v4.0. To our knowledge, this variant is novel and has not been previously reported in the relevant scientific literature or databases. This variant has been observed in trans with a pathogenic variant in an individual with a phenotype consistent with autosomal recessive myotonia congenita (Royal Melbourne Hospital). Computational evidence predicts a deleterious effect for the missense substitution (REVEL = 0.69). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM3, PM2_Supporting, PP3.

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