ClinVar Miner

Submissions for variant NM_001927.4(DES):c.343C>T (p.Leu115Phe)

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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 RCV002594428 SCV002950941 uncertain significance Desmin-related myofibrillar myopathy 2022-07-10 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 115 of the DES protein (p.Leu115Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with cardiac conduction disease (PMID: 31835587). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects DES function (PMID: 31835587). This variant disrupts the p.Leu115 amino acid residue in DES. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 33290826). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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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