Submissions for variant NM_032119.4(ADGRV1):c.7873C>T (p.Arg2625Cys)

gnomAD frequency: 0.00025  dbSNP: rs201583659

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155734	SCV000205444	uncertain significance	not specified	2013-11-06	criteria provided, single submitter	clinical testing	The Arg2625Cys variant in GPR98 has not been previously reported in individuals with hearing loss, but has been identified in 0.2% (1/574) of European chromosom es by the ClinSeq Project (dbSNP rs201583659). Computational analyses (biochemic al amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not p rovide strong support for or against an impact to the protein. In summary, addit ional data is needed to determine the clinical significance of this variant.
Athena Diagnostics Inc	RCV000710462	SCV000840687	uncertain significance	not provided	2018-04-10	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000765844	SCV000897240	uncertain significance	Usher syndrome type 2C; Febrile seizures, familial, 4	2018-10-31	criteria provided, single submitter	clinical testing
Invitae	RCV000710462	SCV001215713	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001157105	SCV001318651	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.
GeneDx	RCV000710462	SCV001786449	likely benign	not provided	2020-12-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002516135	SCV003538243	uncertain significance	Inborn genetic diseases	2021-07-26	criteria provided, single submitter	clinical testing	The c.7873C>T (p.R2625C) alteration is located in exon 33 (coding exon 33) of the ADGRV1 gene. This alteration results from a C to T substitution at nucleotide position 7873, causing the arginine (R) at amino acid position 2625 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003965166	SCV004781414	likely benign	ADGRV1-related condition	2022-08-19	criteria provided, single submitter	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).