Submissions for variant NM_032119.4(ADGRV1):c.2456G>A (p.Ser819Asn)

gnomAD frequency: 0.00014  dbSNP: rs182395524

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000146075	SCV000193257	uncertain significance	Febrile seizures, familial, 4	2013-08-27	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000174607	SCV000225929	likely benign	not specified	2016-09-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000755456	SCV000602451	likely benign	not provided	2017-05-24	criteria provided, single submitter	clinical testing	The p.Ser819Asn variant (rs182395524) has not been previously associated with hearing loss and is listed in the ClinVar database as likely benign or as a variant of uncertain significance (Variation ID: 158650). This variant is listed in the Genome Aggregation Database (gnomAD) browser with a frequency in Latino populations of 0.428% (identified in 147 out of 34,382 chromosomes). The serine at codon 819 is highly conserved (Alamut software v2.9); however, avian species have an asparagine at this position suggesting this change is evolutionary tolerated. Furthermore, due to similar physiochemical properties between serine and asparagine, computational analyses suggest this variant does not have a significant effect on ADGRV1 protein structure/function (SIFT: tolerated, PolyPhen2: benign, and Mutation Taster: polymorphism).Thus, the p.Ser819Asn variant is likely to be benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000174607	SCV000966347	likely benign	not specified	2018-05-08	criteria provided, single submitter	clinical testing	p.Ser819Asn in exon 13 of ADGRV1: This variant is classified as likely benign du e to a lack of conservation across species, including mammals. Of note, rabbit h as an asparagine at this position despite nearby amino acid conservation. In add ition, computational prediction tools do not suggest a high likelihood of impact to the protein. This variant has been identified in 0.4% (147/34382) of Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinsti tute.org; dbSNP rs182395524). ACMG/AMP Criteria applied: BS1_Supporting, BP4
Labcorp Genetics (formerly Invitae), Labcorp	RCV000755456	SCV001690616	likely benign	not provided	2024-01-22	criteria provided, single submitter	clinical testing
GeneDx	RCV000755456	SCV001825898	likely benign	not provided	2021-04-21	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000755456	SCV003820469	uncertain significance	not provided	2019-07-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004551278	SCV004722602	likely benign	ADGRV1-related disorder	2020-01-30	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).