Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001914089 | SCV002192996 | uncertain significance | Cohen syndrome | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with valine at codon 1179 of the VPS13B protein (p.Met1179Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs764040349, gnomAD 0.003%). 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: 1420196). 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: "Benign"; Align-GVGD: "Not Available"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Prevention |
RCV004743653 | SCV005367039 | uncertain significance | VPS13B-related disorder | 2024-09-16 | no assertion criteria provided | clinical testing | The VPS13B c.3535A>G variant is predicted to result in the amino acid substitution p.Met1179Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |