ClinVar Miner

Submissions for variant NM_152393.4(KLHL40):c.601T>C (p.Trp201Arg)

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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 RCV002966773 SCV003283675 uncertain significance Nemaline myopathy 8 2022-01-17 criteria provided, single submitter clinical testing 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. This variant disrupts the p.Trp201 amino acid residue in KLHL40. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23746549). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 disruptive. This variant has not been reported in the literature in individuals affected with KLHL40-related conditions. This variant is present in population databases (rs772612538, gnomAD 0.004%). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 201 of the KLHL40 protein (p.Trp201Arg).

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