ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.7468G>A (p.Ala2490Thr) (rs143632883)

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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 RCV000039629 SCV000063318 uncertain significance not specified 2015-02-26 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Ala2490Thr va riant in GPR98 has been previously reported in 1 individual with hearing loss; h owever a variant affecting the remaining copy of GPR98 was not identified in thi s individual (LMM unpublished data). In addition, this variant has been identifi ed in 30/66628 (0.05%) European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs143632883). The alanine (Ala) res idue at position 2490 is not well conserved in some mammals and most evolutionar y distant species, raising the possibility that a change at this position may be tolerated. Additional computational prediction tools do not provide strong supp ort for or against an impact to the protein. In summary, while the clinical sign ificance of the p.Ala2490Thr variant is uncertain, the conservation data and its frequency in the general population suggest that it is more likely to be benign .
Invitae RCV001057194 SCV001221674 uncertain significance not provided 2019-12-11 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 2490 of the ADGRV1 protein (p.Ala2490Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs143632883, ExAC 0.05%). This variant has not been reported in the literature in individuals with ADGRV1-related disease. ClinVar contains an entry for this variant (Variation ID: 46373). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 RCV001155420 SCV001316846 uncertain significance Usher syndrome, type 2C 2017-04-27 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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