ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.1718G>T (p.Gly573Val) (rs200789563)

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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 RCV000039546 SCV000063235 uncertain significance not specified 2017-07-13 criteria provided, single submitter clinical testing The p.Gly573Val variant in GPR98 has been previously reported in 3 individuals w ith hearing loss (Neveling 2013, LMM data), all of whom also carried the p.Arg31 47Gln variant of unknown significance in GPR98. These two variants were determi ned to be in cis in 1 individual tested at our laboratory. The p.Gly573Val varia nt has also been reported in ClinVar (Variation ID # 46290) as of uncertain sign ificance. The p.Gly573Val variant has been identified in 0.1% (41/34388) of Lati no chromosomes at a similar frequency of the p.Arg3147Gln variant at 0.1% (42/34 390) of Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gn omad.broadinstitute.org; dbSNP rs200789563 and rs200792658). All information col lectively suggests that these variants are in linkage disequilibrium and are lik ely in cis in all of the reported individuals. Although the p.Gly753Val variant has been seen in the general population, its frequency is not high enough to rul e out a pathogenic role. Additionally, computational prediction tools and conser vation analyses do not provide strong support for or against an impact to the pr otein. In summary, the clinical significance of this variant is uncertain.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000513285 SCV000340753 uncertain significance not provided 2017-11-15 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000513285 SCV000609166 uncertain significance not provided 2017-04-01 criteria provided, single submitter clinical testing
Invitae RCV000513285 SCV001235005 uncertain significance not provided 2019-11-29 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 573 of the ADGRV1 protein (p.Gly573Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs200789563, ExAC 0.07%). This variant has been observed in a family affected with progressive hearing loss (PMID: 24123792). ClinVar contains an entry for this variant (Variation ID: 46290). 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: "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 RCV001152886 SCV001314124 uncertain significance Usher syndrome, type 2C 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Sharon lab,Hadassah-Hebrew University Medical Center RCV001002855 SCV001160882 likely pathogenic Usher syndrome type 2 2019-06-23 no assertion criteria provided research

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