ClinVar Miner

Submissions for variant NM_152393.4(KLHL40):c.553G>C (p.Gly185Arg)

gnomAD frequency: 0.00001  dbSNP: rs921432594
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001055719 SCV001220123 uncertain significance Nemaline myopathy 8 2022-04-01 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 185 of the KLHL40 protein (p.Gly185Arg). This variant is present in population databases (no rsID available, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with KLHL40-related conditions. ClinVar contains an entry for this variant (Variation ID: 851342). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV001772270 SCV001992658 uncertain significance not provided 2019-02-13 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); 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
Ambry Genetics RCV003283919 SCV003961251 uncertain significance Inborn genetic diseases 2023-05-04 criteria provided, single submitter clinical testing The c.553G>C (p.G185R) alteration is located in exon 1 (coding exon 1) of the KLHL40 gene. This alteration results from a G to C substitution at nucleotide position 553, causing the glycine (G) at amino acid position 185 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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