ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.16312A>G (p.Thr5438Ala) (rs201890097)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000155118 SCV000204804 likely benign not specified 2013-12-12 criteria provided, single submitter clinical testing Thr5438Ala in Exon 76 of GPR98: This variant is not expected to have clinical si gnificance because it is poorly conserved across species, with two primates (mar moset and squirrel monkey) having an Ala at this position, and computational too ls (amino acid conservation, AlignGVGD, PolyPhen2, and SIFT) do not suggest an i mpact to the protein. In addition, it has been previously reported in one study as a "neutral" variant due to its presence in 4/878 (0.48%) control chromosomes (Le Quesne Stabej 2012), and was also identified in 0.1% (5/8240) of European A merican chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washing ton.edu; dbSNP rs201890097).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724031 SCV000232432 uncertain significance not provided 2016-06-22 criteria provided, single submitter clinical testing
GeneDx RCV000724031 SCV000982959 likely benign not provided 2018-04-09 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Clinical Services Laboratory,Illumina RCV001157635 SCV001319224 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.
Invitae RCV000724031 SCV001415412 uncertain significance not provided 2019-12-12 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 5438 of the ADGRV1 protein (p.Thr5438Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs201890097, ExAC 0.06%). This variant has not been reported in the literature in individuals with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 178372). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine 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.

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