ClinVar Miner

Submissions for variant NM_152393.4(KLHL40):c.1835G>A (p.Arg612Gln)

gnomAD frequency: 0.00004  dbSNP: rs143516959
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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 RCV001300239 SCV001489374 uncertain significance Nemaline myopathy 8 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 612 of the KLHL40 protein (p.Arg612Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs143516959, ExAC 0.06%). This variant has not been reported in the literature in individuals affected with KLHL40-related conditions. 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
GeneDx RCV001773607 SCV001994536 uncertain significance not provided 2019-08-29 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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