Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001968135 | SCV002219792 | uncertain significance | Cohen syndrome | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with phenylalanine at codon 2404 of the VPS13B protein (p.Cys2404Phe). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and phenylalanine. 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: 1442234). 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 expected to disrupt VPS13B protein function with a positive predictive value of 80%. 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. |
Fulgent Genetics, |
RCV001968135 | SCV002778376 | uncertain significance | Cohen syndrome | 2021-08-05 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004744164 | SCV005365898 | uncertain significance | VPS13B-related disorder | 2024-01-22 | no assertion criteria provided | clinical testing | The VPS13B c.7136G>T variant is predicted to result in the amino acid substitution p.Cys2379Phe. To our knowledge, this variant has not been reported in the literature or in gnomAD, 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. |