ClinVar Miner

Submissions for variant NM_017890.4(VPS13B):c.2596G>A (p.Val866Ile) (rs150185067)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224087 SCV000281217 likely benign not provided 2015-06-15 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000303841 SCV000470778 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 RCV000503780 SCV000597881 uncertain significance not specified 2017-05-26 criteria provided, single submitter clinical testing
Invitae RCV000303841 SCV000827451 uncertain significance Cohen syndrome 2019-12-13 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 866 of the VPS13B protein (p.Val866Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs150185067, ExAC 0.1%). This variant has been observed in a cohort of individuals affected with Cohen syndrome (PMID: 16648375). ClinVar contains an entry for this variant (Variation ID: 235550). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000719173 SCV000850039 uncertain significance History of neurodevelopmental disorder 2018-09-29 criteria provided, single submitter clinical testing Insufficient evidence

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