ClinVar Miner

Submissions for variant NM_152393.4(KLHL40):c.1246G>A (p.Val416Met)

gnomAD frequency: 0.00001  dbSNP: rs759198473
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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 RCV001052340 SCV001216547 uncertain significance Nemaline myopathy 8 2022-06-20 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 416 of the KLHL40 protein (p.Val416Met). This variant is present in population databases (rs759198473, gnomAD 0.06%). 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: 848562). 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: "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.
Ambry Genetics RCV002553745 SCV003730711 uncertain significance Inborn genetic diseases 2024-05-07 criteria provided, single submitter clinical testing The c.1246G>A (p.V416M) alteration is located in exon 2 (coding exon 2) of the KLHL40 gene. This alteration results from a G to A substitution at nucleotide position 1246, causing the valine (V) at amino acid position 416 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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