ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.5295C>G (p.Phe1765Leu) (rs201388114)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723731 SCV000202818 uncertain significance not provided 2014-05-05 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000153338 SCV000602443 uncertain significance not specified 2017-01-16 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000153338 SCV000711044 uncertain significance not specified 2017-08-24 criteria provided, single submitter clinical testing The p.Phe1765Leu variant in GPR98 has not been previously reported in individual s with hearing loss, but has been identified in 58/126298 European chromosomes b y the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; db SNP rs201388114). Computational prediction tools and conservation analysis sugge st that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significan ce of the p.Phe1765Leu variant is uncertain.
Invitae RCV000723731 SCV001229287 uncertain significance not provided 2019-12-31 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 1765 of the ADGRV1 protein (p.Phe1765Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs201388114, ExAC 0.04%). This variant has not been reported in the literature in individuals with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 167156). 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.
Illumina Clinical Services Laboratory,Illumina RCV001155223 SCV001316640 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.

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