Submissions for variant NM_152564.5(VPS13B):c.2248A>G (p.Ser750Gly)

gnomAD frequency: 0.00004  dbSNP: rs112858205

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001233612	SCV001406214	uncertain significance	Cohen syndrome	2022-10-25	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 750 of the VPS13B protein (p.Ser750Gly). This variant is present in population databases (rs112858205, gnomAD 0.008%). 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: 960142). 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.
Genetic Services Laboratory, University of Chicago	RCV001819932	SCV002068865	uncertain significance	not specified	2018-04-09	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001233612	SCV002794015	uncertain significance	Cohen syndrome	2021-07-03	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001233612	SCV002079509	uncertain significance	Cohen syndrome	2020-06-21	no assertion criteria provided	clinical testing