Submissions for variant NM_032119.4(ADGRV1):c.1849G>A (p.Val617Met)

gnomAD frequency: 0.00046  dbSNP: rs199988872

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000725781	SCV000168739	likely benign	not provided	2020-05-13	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26969326)
Eurofins Ntd Llc (ga)	RCV000725781	SCV000339340	uncertain significance	not provided	2016-02-12	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000125295	SCV000711038	likely benign	not specified	2017-04-20	criteria provided, single submitter	clinical testing	p.Val617Met in exon 10 of GPR98: This variant is not expected to have clinical s ignificance because it has been identified in 0.3% (28/10044) of Ashkenazi Jewis h chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadins titute.org; dbSNP rs199988872).
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000725781	SCV000884982	uncertain significance	not provided	2017-12-29	criteria provided, single submitter	clinical testing	The ADGRV1 p.Val617Met variant (rs199988872) was reported in one individual with a diagnosis of Usher syndrome type 2C who also harbored the ADGRV1 p.Ile2332Phe variant (Sloan-Heggen 2016). The p.Val617Met variant is listed in the Genome Aggregation Database (gnomAD) with an allele frequency of 0.3 percent in the Ashkenazi Jewish population (identified on 28 out of 10,044 chromosomes) and has been reported to the ClinVar database (Variation ID: 137500). The valine at position 617 is highly conserved considering 12 species up to zebrafish (Alamut software v2.10.0), and computational analyses predict conflicting effects of this variant on protein structure/function (SIFT: damaging, GVGD: class C0, PolyPhen-2: possibly damaging). Altogether, there is not enough evidence to classify the p.Val617Met variant with certainty.
Mendelics	RCV000987533	SCV001136848	uncertain significance	Usher syndrome type 2C	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000987533	SCV001314128	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000725781	SCV001730668	benign	not provided	2025-01-13	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000725781	SCV004159098	uncertain significance	not provided	2023-09-01	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000725781	SCV001954473	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000725781	SCV001974439	uncertain significance	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004737211	SCV005352725	likely benign	ADGRV1-related disorder	2024-08-07	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).