ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.9440G>A (p.Arg3147Gln) (rs200792658)

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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 RCV000039660 SCV000063349 uncertain significance not specified 2018-08-02 criteria provided, single submitter clinical testing The p.Arg3147Gln variant in ADGRV1 (also known as GPR98) has been previously rep orted in 4 individuals with hearing loss (Neveling 2013, LMM data), all of whom also carried the p.Gly573Val variant of uncertain significance in ADGRV1. These two variants were determined to be in cis in 2 individuals tested at our laborat ory. The p.Arg3147Gln variant has also been reported in ClinVar (Variation ID # 46404) as of uncertain significance. It has also been identified in 0.1% (42/343 90) of Latino chromosomes at a similar frequency as the p.Arg3147Gln variant (0. 1%; 41/34388 Latino chromosomes) by the Genome Aggregation Database (gnomAD, htt p://gnomad.broadinstitute.org; dbSNP rs200792658 and dbSNP rs200789563). Collect ively, these data suggest that these variants are in linkage disequilibrium and are in cis in all reported individuals identified thus far. Moreover, arginine ( Arg) at position 3147 is not conserved in mammals or evolutionarily distant spec ies. Of note, 2 mammals (Elephant and Opossum) carry a glutamine (Gln) at this p osition, raising the possibility that this change may be tolerated. Additional c omputational prediction tools do not provide strong support for or against an im pact to the protein. In summary, the clinical significance of the p.Arg3147Gln v ariant is uncertain. ACMG/AMP criteria applied: PM2_Supporting, BP4.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000512737 SCV000340755 uncertain significance not provided 2017-11-24 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000512737 SCV000609167 uncertain significance not provided 2017-03-01 criteria provided, single submitter clinical testing
Invitae RCV000512737 SCV001198366 uncertain significance not provided 2019-11-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 3147 of the ADGRV1 protein (p.Arg3147Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs200792658, ExAC 0.08%). This variant has been observed in a family affected with progressive hearing loss (PMID: 24123792). ClinVar contains an entry for this variant (Variation ID: 46404). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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 RCV001157220 SCV001318771 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 RCV001002856 SCV001160883 likely pathogenic Usher syndrome type 2 2019-06-23 no assertion criteria provided research

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