Submissions for variant NM_152564.5(VPS13B):c.3656C>G (p.Ser1219Cys)

gnomAD frequency: 0.00073  dbSNP: rs149478021

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000393627	SCV000341970	uncertain significance	not provided	2016-06-16	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079914	SCV001104284	likely benign	Cohen syndrome	2025-01-29	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001820832	SCV002069490	uncertain significance	not specified	2021-12-20	criteria provided, single submitter	clinical testing	DNA sequence analysis of the VPS13B gene demonstrated a sequence change, c.3656C>G, in exon 24 that results in an amino acid change, p.Ser1219Cys. This sequence change does not appear to have been previously described in individuals with VPS13B-related disorders. This sequence change has been described in the gnomAD database with a frequency of 0.21% in the African/African American subpopulation and includes one homozygous individual (dbSNP rs149478021). The p.Ser1219Cys change affects a moderately conserved amino acid residue located in a domain of the VPS13B protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Ser1219Cys substitution. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Ser1219Cys change remains unknown at this time.
Ambry Genetics	RCV002348015	SCV002618957	uncertain significance	Inborn genetic diseases	2018-01-03	criteria provided, single submitter	clinical testing	The p.S1219C variant (also known as c.3656C>G), located in coding exon 23 of the VPS13B gene, results from a C to G substitution at nucleotide position 3656. The serine at codon 1219 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV001079914	SCV003820445	uncertain significance	Cohen syndrome	2021-06-05	criteria provided, single submitter	clinical testing
GeneDx	RCV000393627	SCV005376687	uncertain significance	not provided	2023-10-24	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc.	RCV001079914	SCV002082520	benign	Cohen syndrome	2019-11-11	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003920136	SCV004729212	likely benign	VPS13B-related disorder	2022-04-14	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).