Submissions for variant NM_032119.4(ADGRV1):c.13919G>A (p.Gly4640Glu)

gnomAD frequency: 0.00003  dbSNP: rs727504706

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155990	SCV000205702	uncertain significance	not specified	2016-11-30	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Gly4640Glu va riant in GPR8 has been previously reported in one individual with Usher syndrome (Le Quesne Stabej 2012) and was identified by our laboratory in three individua ls with hearing loss; however, this variant was not thought to be related to the clinical features in these individuals due to the presence of an alternate expl anation of the hearing loss and/or non-segregation with disease in affected fami ly members. Data from large population studies are insufficient to assess the fr equency of this variant. Computational prediction tools and conservation analysi s suggest that the p.Gly4640Glu variant may impact the protein, though this info rmation is not predictive enough to determine pathogenicity. In summary, the cli nical significance of the p.Gly4640Glu variant is uncertain; however, based on t he identification of this variant in several individuals with an alternate expla nation for their hearing loss suggests that it is more likely to be benign.
Eurofins Ntd Llc (ga)	RCV000725333	SCV000336110	uncertain significance	not provided	2015-10-16	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000725333	SCV001421516	uncertain significance	not provided	2022-06-14	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 4640 of the ADGRV1 protein (p.Gly4640Glu). This variant is present in population databases (rs727504706, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 179204). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV003989333	SCV004806520	uncertain significance	Febrile seizures, familial, 4	2024-03-26	criteria provided, single submitter	clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV000725333	SCV005199498	uncertain significance	not provided	2022-05-27	criteria provided, single submitter	clinical testing
Paris Brain Institute, Inserm - ICM	RCV001839411	SCV001810134	likely pathogenic	Idiopathic generalized epilepsy		no assertion criteria provided	research