Submissions for variant NM_152564.5(VPS13B):c.1248G>T (p.Gln416His)

gnomAD frequency: 0.00111  dbSNP: rs143024324

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000711290	SCV000113813	uncertain significance	not provided	2014-12-20	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000081878	SCV000597873	uncertain significance	not specified	2016-06-24	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001082583	SCV000755435	likely benign	Cohen syndrome	2025-01-30	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000711290	SCV000841627	uncertain significance	not provided	2017-10-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000623758	SCV000848156	uncertain significance	Inborn genetic diseases	2018-01-30	criteria provided, single submitter	clinical testing	The p.Q416H variant (also known as c.1248G>T), located in coding exon 8 of the VPS13B gene, results from a G to T substitution at nucleotide position 1248. The glutamine at codon 416 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Illumina Laboratory Services, Illumina	RCV001082583	SCV001323817	uncertain significance	Cohen syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001082583	SCV001468402	uncertain significance	Cohen syndrome	2021-03-30	criteria provided, single submitter	clinical testing	VPS13B NM_152564.4 exon 9 p.Gln416His (c.1248G>T): This variant has not been reported in the literature but is present in 0.4% (45/10348) of Ashkenazi Jewish alleles in the Genome Aggregation Database https://gnomad.broadinstitute.org/variant/8-100146901-G-T). This variant is present in ClinVar (Variation ID:95831). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Laboratoire de Génétique Moléculaire, CHU Bordeaux	RCV000711290	SCV001468935	likely benign	not provided	2023-12-05	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001082583	SCV001529777	uncertain significance	Cohen syndrome	2018-03-20	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	RCV001082583	SCV001653322	uncertain significance	Cohen syndrome	2021-05-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000711290	SCV001770313	uncertain significance	not provided	2020-04-21	criteria provided, single submitter	clinical testing	Identified as heterozygous via exome sequencing in a sibling of an individual with autism (Yu et al., 2013); Identified as heterozgyous via exome sequencing for carrier screening for autosomal recessive conditions in a healthy individual (Mehrjoo et al., 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26443248, 23352163)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000711290	SCV002011570	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001082583	SCV003925082	uncertain significance	Cohen syndrome	2022-04-11	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003935062	SCV004747452	likely benign	VPS13B-related disorder	2021-09-02	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).