Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000634099 | SCV000755377 | uncertain significance | Cohen syndrome | 2022-10-12 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2822 of the VPS13B protein (p.Tyr2822Cys). This variant is present in population databases (rs371325199, gnomAD 0.01%). This missense change has been observed in individual(s) with Cohen syndrome (PMID: 16648375). ClinVar contains an entry for this variant (Variation ID: 528842). 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. |
Ambry Genetics | RCV002529820 | SCV003719418 | uncertain significance | Inborn genetic diseases | 2022-02-26 | criteria provided, single submitter | clinical testing | The c.8465A>G (p.Y2822C) alteration is located in exon 46 (coding exon 45) of the VPS13B gene. This alteration results from a A to G substitution at nucleotide position 8465, causing the tyrosine (Y) at amino acid position 2822 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Mayo Clinic Laboratories, |
RCV004791649 | SCV005409500 | uncertain significance | not provided | 2023-12-06 | criteria provided, single submitter | clinical testing | BP1 |
Natera, |
RCV000634099 | SCV001460982 | uncertain significance | Cohen syndrome | 2020-09-16 | no assertion criteria provided | clinical testing | |
Prevention |
RCV003905701 | SCV004722377 | uncertain significance | VPS13B-related disorder | 2024-02-27 | no assertion criteria provided | clinical testing | The VPS13B c.8390A>G variant is predicted to result in the amino acid substitution p.Tyr2797Cys. This variant has been reported in an individual with Cohen syndrome, but no additional studies were performed to help assess its pathogenicity (Seifert et al 2006. PubMed ID: 16648375). This variant is reported in 0.011% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |