ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.16999A>G (p.Met5667Val) (rs201767389)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000825096 SCV000966350 likely benign not specified 2018-02-13 criteria provided, single submitter clinical testing p.Met5667Val in exon 78 of ADGRV1: This variant is not expected to have clinical significance due to a lack of conservation across species. Of note, over 30 mam mals, including one primate, have a valine at this position despite high nearby amino acid conservation. In addition, computational prediction tools do not sugg est a high likelihood of impact to the protein. This variant has been identified in 12/95060 European chromosomes by the Genome Aggregation Database (gnomAD, ht tp://gnomad.broadinstitute.org; dbSNP rs201767389). ACMG/AMP Criteria applied: B P4_Strong (Richards 2015).
Illumina Clinical Services Laboratory,Illumina RCV001152170 SCV001313377 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 RCV001364432 SCV001560581 uncertain significance not provided 2020-08-26 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 5667 of the ADGRV1 protein (p.Met5667Val). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs201767389, ExAC 0.01%). This variant has not been reported in the literature in individuals with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 666642). 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 valine 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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