Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001069351 | SCV001234513 | uncertain significance | Cohen syndrome | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with alanine at codon 312 of the VPS13B protein (p.Thr312Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs780702951, gnomAD 0.04%). 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: 862601). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt VPS13B protein function. 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. |
Baylor Genetics | RCV001069351 | SCV001522892 | uncertain significance | Cohen syndrome | 2023-07-21 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001069351 | SCV001466470 | likely benign | Cohen syndrome | 2020-09-18 | no assertion criteria provided | clinical testing | |
Prevention |
RCV004743283 | SCV005345033 | uncertain significance | VPS13B-related disorder | 2024-05-07 | no assertion criteria provided | clinical testing | The VPS13B c.934A>G variant is predicted to result in the amino acid substitution p.Thr312Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.036% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |