Submissions for variant NM_032119.4(ADGRV1):c.4171G>A (p.Glu1391Lys)

gnomAD frequency: 0.00004  dbSNP: rs766007827

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001156789	SCV001318315	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV001195223	SCV001365530	uncertain significance	not specified	2019-08-14	criteria provided, single submitter	clinical testing	The p.Glu139Lys variant in ADGRV1 has not been previously reported in individuals with Usher syndrone but has been identified in 0.2% (43/19396) of East Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: BS1_Supporting.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001236644	SCV001409376	likely benign	not provided	2024-09-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004738173	SCV005360397	likely benign	ADGRV1-related disorder	2024-07-16	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).