Submissions for variant NM_152564.5(VPS13B):c.1639A>G (p.Thr547Ala)

gnomAD frequency: 0.00022  dbSNP: rs142971568

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000415954	SCV000493319	uncertain significance	not provided	2016-08-01	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000501800	SCV000597914	uncertain significance	not specified	2015-10-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000501800	SCV000714722	likely benign	not specified	2018-01-09	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV001084311	SCV001025221	likely benign	Cohen syndrome	2024-01-22	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001084311	SCV001325778	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.
Ambry Genetics	RCV002402111	SCV002709274	uncertain significance	Inborn genetic diseases	2020-05-12	criteria provided, single submitter	clinical testing	The p.T547A variant (also known as c.1639A>G), located in coding exon 11 of the VPS13B gene, results from an A to G substitution at nucleotide position 1639. The threonine at codon 547 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and alanine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003972559	SCV004795937	likely benign	VPS13B-related disorder	2021-07-19	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.	RCV001084311	SCV002079477	benign	Cohen syndrome	2019-10-21	no assertion criteria provided	clinical testing