Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Genomics, |
RCV000768366 | SCV000899087 | uncertain significance | Cohen syndrome | 2021-03-30 | criteria provided, single submitter | clinical testing | VPS13B NM_017890 exon 56 p.Thr3415Ile (c.10244C>T): This variant has not been reported in the literature but is present in 4/17248 East Asian alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs767783667). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Labcorp Genetics |
RCV000768366 | SCV002204133 | uncertain significance | Cohen syndrome | 2022-07-19 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 3415 of the VPS13B protein (p.Thr3415Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs767783667, gnomAD 0.02%). 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: 626207). 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. |