Submissions for variant NM_152564.5(VPS13B):c.572A>G (p.Asp191Gly)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002914246	SCV003259301	uncertain significance	Cohen syndrome	2022-11-01	criteria provided, single submitter	clinical testing	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. 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. This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. This variant is present in population databases (rs780314838, gnomAD 0.003%). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 191 of the VPS13B protein (p.Asp191Gly).
Ambry Genetics	RCV002914245	SCV003571190	uncertain significance	Inborn genetic diseases	2021-07-26	criteria provided, single submitter	clinical testing	The c.572A>G (p.D191G) alteration is located in exon 5 (coding exon 4) of the VPS13B gene. This alteration results from a A to G substitution at nucleotide position 572, causing the aspartic acid (D) at amino acid position 191 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.