ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.11197C>A (p.Leu3733Met)

gnomAD frequency: 0.00001  dbSNP: rs1318142770
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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 RCV001065674 SCV001230644 uncertain significance Cohen syndrome 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces leucine with methionine at codon 3758 of the VPS13B protein (p.Leu3758Met). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and methionine. 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. 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: "Possibly Damaging"; Align-GVGD: "Class Not Available"). This variant has not been reported in the literature in individuals with VPS13B-related conditions. This variant is not present in population databases (ExAC no frequency).
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001065674 SCV005402365 uncertain significance Cohen syndrome 2023-11-29 criteria provided, single submitter clinical testing The VPS13B c.11197C>A (p.Leu3733Met) missense change has a maximum subpopulation frequency of 0.0058% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with Cohen syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
GeneDx RCV004820147 SCV005441226 uncertain significance not provided 2024-06-25 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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