ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.12181G>T (p.Val4061Phe) (rs200816323)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000150777 SCV000198274 uncertain significance not specified 2013-08-01 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Val4061Phe vari ant in GPR98 has been previously reported in one individual with hearing loss by our laboratory; however, a second variant in GPR98 was not identified in this i ndividual. The Val4061Phe variant has been also been identified in 0.1% (14/8220 ) of European American chromosomes by the NHLBI Exome Sequencing Project (http:/ /; dbSNP rs200816323); however this frequency is not h igh enough to rule out pathogenicity. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide st rong support for or against an impact to the protein. In summary, the clinical s ignificance of this variant cannot be determined with certainty; however, based upon its frequency in the general population, we lean towards a more likely beni gn role.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000729114 SCV000856753 uncertain significance not provided 2017-09-01 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765850 SCV000897246 uncertain significance Usher syndrome, type 2C; Febrile seizures, familial, 4 2018-10-31 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000729114 SCV001142919 uncertain significance not provided 2018-12-18 criteria provided, single submitter clinical testing
Invitae RCV000729114 SCV001232323 uncertain significance not provided 2019-11-29 criteria provided, single submitter clinical testing This sequence change replaces valine with phenylalanine at codon 4061 of the ADGRV1 protein (p.Val4061Phe). The valine residue is moderately conserved and there is a small physicochemical difference between valine and phenylalanine. This variant is present in population databases (rs200816323, ExAC 0.2%). This variant has not been reported in the literature in individuals with ADGRV1-related disease. ClinVar contains an entry for this variant (Variation ID: 163601). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; 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.
Illumina Clinical Services Laboratory,Illumina RCV001153111 SCV001314366 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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