Submissions for variant NM_032119.4(ADGRV1):c.12181G>T (p.Val4061Phe)

gnomAD frequency: 0.00061  dbSNP: rs200816323

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000150777	SCV000198274	uncertain significance	not specified	2013-08-01	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Val4061Phe vari ant in GPR98 has been previously reported in one individual with hearing loss by our laboratory; however, a second variant in GPR98 was not identified in this i ndividual. The Val4061Phe variant has been also been identified in 0.1% (14/8220 ) of European American chromosomes by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS/; dbSNP rs200816323); however this frequency is not h igh enough to rule out pathogenicity. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide st rong support for or against an impact to the protein. In summary, the clinical s ignificance of this variant cannot be determined with certainty; however, based upon its frequency in the general population, we lean towards a more likely beni gn role.
Eurofins Ntd Llc (ga)	RCV000729114	SCV000856753	uncertain significance	not provided	2017-09-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000765850	SCV000897246	uncertain significance	Usher syndrome type 2C; Febrile seizures, familial, 4	2018-10-31	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000729114	SCV001142919	uncertain significance	not provided	2018-12-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000729114	SCV001232323	benign	not provided	2025-01-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001153111	SCV001314366	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.
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center	RCV001375219	SCV001571921	likely benign	Hearing impairment	2021-04-12	criteria provided, single submitter	clinical testing	BS1_Supporting, BP4_Supporting
GeneDx	RCV000729114	SCV001782660	likely benign	not provided	2020-03-23	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 32707200)
GenomeConnect - Invitae Patient Insights Network	RCV001153111	SCV001749463	not provided	Usher syndrome type 2C		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 12-01-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.
Clinical Genetics, Academic Medical Center	RCV000729114	SCV001919286	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000729114	SCV001926933	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000729114	SCV001970138	likely benign	not provided		no assertion criteria provided	clinical testing