Submissions for variant NM_152564.5(VPS13B):c.710G>A (p.Arg237His)

gnomAD frequency: 0.00001  dbSNP: rs751804274

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000701576	SCV000830383	uncertain significance	Cohen syndrome	2022-10-25	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 237 of the VPS13B protein (p.Arg237His). This variant is present in population databases (rs751804274, gnomAD 0.01%). This missense change has been observed in individual(s) with developmental disorder (PMID: 32959227). ClinVar contains an entry for this variant (Variation ID: 578539). 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. 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.
Natera, Inc.	RCV000701576	SCV002079443	uncertain significance	Cohen syndrome	2019-11-11	no assertion criteria provided	clinical testing