ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.13382A>G (p.His4461Arg) (rs182698253)

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Total submissions: 6
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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 RCV000433926 SCV000511023 uncertain significance not provided 2016-06-27 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000507824 SCV000602446 uncertain significance not specified 2017-01-26 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000507824 SCV000711055 uncertain significance not specified 2017-03-28 criteria provided, single submitter clinical testing The p.His4461Arg variant in GPR98 has not been previously reported in individual s with hearing loss, but has been identified in 7/66510 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 182698253). Although this variant has been seen in the general population, its f requency is not high enough to rule out a pathogenic role. Computational predict ion tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.His446 1Arg variant is uncertain.
Fulgent Genetics,Fulgent Genetics RCV000765855 SCV000897251 uncertain significance Usher syndrome, type 2C; Febrile seizures, familial, 4 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001153219 SCV001314492 uncertain significance Usher syndrome, type 2C 2018-01-12 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.
Invitae RCV000433926 SCV001380554 uncertain significance not provided 2019-10-30 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 4461 of the ADGRV1 protein (p.His4461Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is present in population databases (rs182698253, ExAC 0.02%). This variant has not been reported in the literature in individuals with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 376988). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.

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