Submissions for variant NM_032119.4(ADGRV1):c.14761G>A (p.Ala4921Thr)

gnomAD frequency: 0.00060  dbSNP: rs200115167

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155116	SCV000204802	likely benign	not specified	2013-04-24	criteria provided, single submitter	clinical testing	Ala4921Thr in exon 72 of GPR98: This variant is not expected to have clinical si gnificance because it has been identified in 0.1% (8/8218) of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/ EVS/; dbSNP rs200115167). Furthermore, this amino acid is not well conserved acr oss species and several mammals carry a threonine (Thr) at this position.
Eurofins Ntd Llc (ga)	RCV000724660	SCV000232408	uncertain significance	not provided	2015-03-20	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000724660	SCV001157334	uncertain significance	not provided	2022-09-13	criteria provided, single submitter	clinical testing	The ADGRV1 c.14761G>A; p.Ala4921Thr variant (rs200115167), to our knowledge, has not been reported in the medical literature; however, it is listed in the ClinVar database with conflicting interpretations of pathogenicity (Variation ID: 178370). This variant is found in the general population with an allele frequency in non-Finnish European populations of 0.00% (101/128,320 alleles) in the Genome Aggregation Database. The alanine at codon 4921 is moderately conserved (Alamut v.2.11) and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, based on the available information, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000724660	SCV001222928	likely benign	not provided	2025-01-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002514982	SCV003701881	uncertain significance	Inborn genetic diseases	2021-07-09	criteria provided, single submitter	clinical testing	The c.14761G>A (p.A4921T) alteration is located in exon 72 (coding exon 72) of the ADGRV1 gene. This alteration results from a G to A substitution at nucleotide position 14761, causing the alanine (A) at amino acid position 4921 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV000724660	SCV005687952	uncertain significance	not provided	2024-07-30	criteria provided, single submitter	clinical testing	Identified in a patient with blindness due to alterations of the retina, choroid, vitreous, and/or optic nerve in published literature, however additional patient information was not provided (PMID: 32483926); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25468891, 25683121, 35593993, 32483926)
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000724660	SCV001932157	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000724660	SCV001969446	likely benign	not provided		no assertion criteria provided	clinical testing