Submissions for variant NM_032119.4(ADGRV1):c.13382A>G (p.His4461Arg)

gnomAD frequency: 0.00017  dbSNP: rs182698253

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000433926	SCV000511023	uncertain significance	not provided	2016-06-27	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000433926	SCV000602446	uncertain significance	not provided	2023-11-22	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000507824	SCV000711055	uncertain significance	not specified	2017-03-28	criteria provided, single submitter	clinical testing	The p.His4461Arg variant in GPR98 has not been previously reported in individual s with hearing loss, but has been identified in 7/66510 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 182698253). Although this variant has been seen in the general population, its f requency is not high enough to rule out a pathogenic role. Computational predict ion tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.His446 1Arg variant is uncertain.
Fulgent Genetics, Fulgent Genetics	RCV000765855	SCV000897251	uncertain significance	Usher syndrome type 2C; Febrile seizures, familial, 4	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001153219	SCV001314492	uncertain significance	Usher syndrome type 2C	2018-01-12	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	RCV000433926	SCV001380554	likely benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000433926	SCV002005157	uncertain significance	not provided	2019-04-11	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV004022266	SCV004861612	uncertain significance	Inborn genetic diseases	2022-01-18	criteria provided, single submitter	clinical testing	The c.13382A>G (p.H4461R) alteration is located in exon 66 (coding exon 66) of the ADGRV1 gene. This alteration results from a A to G substitution at nucleotide position 13382, causing the histidine (H) at amino acid position 4461 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000433926	SCV001741330	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000433926	SCV001929341	uncertain significance	not provided		no assertion criteria provided	clinical testing