Submissions for variant NM_152564.5(VPS13B):c.1559A>G (p.His520Arg)

gnomAD frequency: 0.00068  dbSNP: rs143205296

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000426832	SCV000225382	uncertain significance	not provided	2015-04-07	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000239145	SCV000297277	uncertain significance	not specified	2015-11-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000375746	SCV000470768	uncertain significance	Cohen syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000426832	SCV000511792	likely benign	not provided	2016-12-09	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Invitae	RCV000375746	SCV000755419	likely benign	Cohen syndrome	2024-01-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000426832	SCV000780921	uncertain significance	not provided	2018-07-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000375746	SCV001529778	uncertain significance	Cohen syndrome	2018-01-01	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genome-Nilou Lab	RCV000375746	SCV001652732	uncertain significance	Cohen syndrome	2021-05-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000426832	SCV001823659	likely benign	not provided	2018-08-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002399624	SCV002704401	uncertain significance	Inborn genetic diseases	2020-01-29	criteria provided, single submitter	clinical testing	The p.H520R variant (also known as c.1559A>G), located in coding exon 10 of the VPS13B gene, results from an A to G substitution at nucleotide position 1559. The histidine at codon 520 is replaced by arginine, an amino acid with highly similar 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	RCV000375746	SCV003820423	uncertain significance	Cohen syndrome	2022-06-08	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003982923	SCV004796295	likely benign	VPS13B-related disorder	2022-01-28	criteria provided, single submitter	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).
Natera, Inc.	RCV000375746	SCV001454806	likely benign	Cohen syndrome	2020-09-16	no assertion criteria provided	clinical testing