ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.10508C>A (p.Pro3503His)

gnomAD frequency: 0.00001  dbSNP: rs773013716
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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 RCV001933723 SCV002199548 uncertain significance Cohen syndrome 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces proline with histidine at codon 3528 of the VPS13B protein (p.Pro3528His). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and histidine. This variant is present in population databases (rs773013716, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1427471). 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: "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.
Ambry Genetics RCV002561381 SCV003683113 uncertain significance Inborn genetic diseases 2022-09-08 criteria provided, single submitter clinical testing The c.10583C>A (p.P3528H) alteration is located in exon 56 (coding exon 55) of the VPS13B gene. This alteration results from a C to A substitution at nucleotide position 10583, causing the proline (P) at amino acid position 3528 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003911106 SCV004723928 uncertain significance VPS13B-related disorder 2024-02-12 no assertion criteria provided clinical testing The VPS13B c.10508C>A variant is predicted to result in the amino acid substitution p.Pro3503His. This variant can be described as c.10583C>A (p.Pro3528His) using an alternate transcript (NM_017890). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.087% of alleles in individuals of Latino descent in gnomAD, which is likely too common for an undocumented disease-causing variant. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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