Submissions for variant NM_032119.4(ADGRV1):c.9440G>A (p.Arg3147Gln)

gnomAD frequency: 0.00036  dbSNP: rs200792658

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039660	SCV000063349	uncertain significance	not specified	2020-06-04	criteria provided, single submitter	clinical testing	The p.Arg3147Gln variant in ADGRV1 (also known as GPR98) has been previously reported in 5 individuals with hearing loss (Neveling 2013, LMM data), 4 of whom also carried the p.Gly573Val variant of uncertain significance in ADGRV1. These two variants were determined to be in cis in 1 individual tested at our laboratory. The p.Arg3147Gln variant has also been reported in ClinVar (Variation ID # 46404) as of uncertain significance. It has also been identified in 0.1% (42/35316) of Latino chromosomes at a similar frequency as the p.Gly573Val variant (0.1%; 41/35348 Latino chromosomes) by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs200792658 and dbSNP rs200789563). Collectively, these data suggest that these variants are in linkage disequilibrium and are in cis in all reported individuals identified thus far. Moreover, arginine (Arg) at position 3147 is not conserved in mammals or evolutionarily distant species. Of note, 2 mammals (Elephant and Opossum) carry a glutamine (Gln) at this position, raising the possibility that this change may be tolerated. Additional computational prediction tools do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Arg3147Gln variant is uncertain. ACMG/AMP criteria applied: BS1_Supporting, BP4.
Eurofins Ntd Llc (ga)	RCV000512737	SCV000340755	uncertain significance	not provided	2017-11-24	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000512737	SCV000609167	uncertain significance	not provided	2017-03-01	criteria provided, single submitter	clinical testing
Invitae	RCV000512737	SCV001198366	likely benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001157220	SCV001318771	uncertain significance	Usher syndrome type 2C	2017-04-28	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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001002856	SCV001160883	likely pathogenic	Usher syndrome type 2	2019-06-23	no assertion criteria provided	research
Paris Brain Institute, Inserm - ICM	RCV001839410	SCV001810136	likely pathogenic	Idiopathic generalized epilepsy		no assertion criteria provided	research