ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.4337G>A (p.Arg1446Gln)

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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 RCV002957690 SCV003272561 uncertain significance Cohen syndrome 2022-09-01 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1471 of the VPS13B protein (p.Arg1471Gln). This variant is present in population databases (rs756140213, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with VPS13B-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: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003155498 SCV003844717 uncertain significance not specified 2023-02-14 criteria provided, single submitter clinical testing Variant summary: VPS13B c.4412G>A (p.Arg1471Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251150 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.4412G>A in individuals affected with Cohen Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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