ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.4507G>A (p.Ala1503Thr) (rs201391886)

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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 RCV000155106 SCV000204792 uncertain significance not specified 2018-03-21 criteria provided, single submitter clinical testing The p.Ala1503Thr variant in ADGRV1 has been previously identified by our laborat ory in two individuals with hearing loss; however a variant affecting the remain ing copy of ADGRV1 was not identified in either individual. This variant has bee n identified in 56/126586 European chromosomes by the Genome Aggregation Databas e (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs201391886) and is reported in ClinVar (Variation ID: 110040). Although this variant has been seen in the g eneral population, its frequency is not high enough to rule out a pathogenic rol e. Computational prediction tools and conservation analysis do not provide stron g support for or against an impact to the protein. In summary, the clinical sign ificance of the p.Ala1503Thr variant is uncertain. ACMG/AMP Criteria applied: No ne.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000488366 SCV000227849 uncertain significance not provided 2014-11-14 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000488366 SCV000575431 uncertain significance not provided 2016-10-31 criteria provided, single submitter clinical testing
Invitae RCV000488366 SCV001212546 uncertain significance not provided 2019-12-22 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1503 of the ADGRV1 protein (p.Ala1503Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs201391886, ExAC 0.04%). This variant has not been reported in the literature in individuals with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 110040). 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: "Possibly 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 RCV001151340 SCV001312461 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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