Submissions for variant NM_152564.5(VPS13B):c.7995C>G (p.Phe2665Leu)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003108333	SCV003780478	uncertain significance	Cohen syndrome	2022-09-27	criteria provided, single submitter	clinical testing	This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2690 of the VPS13B protein (p.Phe2690Leu). This variant is present in population databases (rs149017920, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV004790473	SCV005409499	uncertain significance	not provided	2024-09-23	criteria provided, single submitter	clinical testing	BP1
PreventionGenetics, part of Exact Sciences	RCV003936695	SCV004756268	uncertain significance	VPS13B-related disorder	2024-01-30	no assertion criteria provided	clinical testing	The VPS13B c.7995C>G variant is predicted to result in the amino acid substitution p.Phe2665Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.048% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.