Submissions for variant NM_152564.5(VPS13B):c.365C>T (p.Pro122Leu)

gnomAD frequency: 0.00013  dbSNP: rs201723380

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000363716	SCV000470759	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.
Genetic Services Laboratory, University of Chicago	RCV000500780	SCV000597871	uncertain significance	not specified	2015-12-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002314081	SCV000848610	uncertain significance	Inborn genetic diseases	2017-01-10	criteria provided, single submitter	clinical testing	The p.P122L variant (also known as c.365C>T), located in coding exon 3 of the VPS13B gene, results from a C to T substitution at nucleotide position 365. The proline at codon 122 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available 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.
Invitae	RCV000363716	SCV001098109	likely benign	Cohen syndrome	2024-01-23	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003401375	SCV004119211	uncertain significance	VPS13B-related disorder	2023-09-06	criteria provided, single submitter	clinical testing	The VPS13B c.365C>T variant is predicted to result in the amino acid substitution p.Pro122Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.13% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-100108613-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.