Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Human Developmental Genetics, |
RCV001257289 | SCV001433835 | uncertain significance | Pituitary stalk interruption syndrome | 2020-04-01 | criteria provided, single submitter | research | |
Labcorp Genetics |
RCV001879967 | SCV002223747 | uncertain significance | Cohen syndrome | 2022-09-06 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1433 of the VPS13B protein (p.Ser1433Cys). This variant is not present in population databases (gnomAD no frequency). 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: 978572). 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"). 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 |
RCV003416133 | SCV004117307 | uncertain significance | VPS13B-related disorder | 2023-04-25 | criteria provided, single submitter | clinical testing | The VPS13B c.4298C>G variant is predicted to result in the amino acid substitution p.Ser1433Cys. This variant was reported in an individual with pituitary stalk interruption syndrome, however a second plausible causative variant in VPS13B was not identified and the individual also had a missense variant in ARID1B (Patient 13 in Table 2, Brauner et al. 2020. PubMed ID: 33270637). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |