Submissions for variant NM_152564.5(VPS13B):c.6905A>G (p.Tyr2302Cys)

dbSNP: rs1833105159

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001242959	SCV001416085	uncertain significance	Cohen syndrome	2022-07-11	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2327 of the VPS13B protein (p.Tyr2327Cys). ClinVar contains an entry for this variant (Variation ID: 967936). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function.
PreventionGenetics, part of Exact Sciences	RCV003973161	SCV004789435	uncertain significance	VPS13B-related disorder	2024-02-21	no assertion criteria provided	clinical testing	The VPS13B c.6905A>G variant is predicted to result in the amino acid substitution p.Tyr2302Cys. To our knowledge, this variant has not been reported in the literature or in a large population database, 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.