ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.8651T>C (p.Val2884Ala) (rs111033517)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000039651 SCV000063340 likely benign not specified 2010-02-03 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000039651 SCV000297335 uncertain significance not specified 2015-08-10 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001154704 SCV001316084 uncertain significance Usher syndrome, type 2C 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000039651 SCV001774676 uncertain significance not specified 2021-07-19 criteria provided, single submitter clinical testing Variant summary: ADGRV1 c.8651T>C (p.Val2884Ala) results in a non-conservative amino acid change located in the Na-Ca exchanger/integrin-beta4 domain (IPR003644) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 248472 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in ADGRV1 causing Usher Syndrome (6e-05 vs 0.0054), allowing no conclusion about variant significance. c.8651T>C has been reported in the literature in at least one individual with a clinical diagnosis of Usher syndrome (Sloan-Heggen_2016). The data does not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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