ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.9643G>A (p.Glu3215Lys) (rs199499672)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000039662 SCV000063351 uncertain significance not specified 2018-01-25 criteria provided, single submitter clinical testing The p.Glu3215Lys variant in ADGRV1 has been previously reported by our laborator y in 2 individuals with hearing loss, one of whom also harbored a second ADGRV1 variant of uncertain significance (trans/cis not yet determined). The variant wa s also identified in 51/126478 European chromosomes by the Genome Aggregation Da tabase (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs199499672). However, t his frequency is not high enough to rule out a pathogenic role. Computational pr ediction tools and conservation analysis suggest that this variant may impact th e protein, though this information is not predictive enough to determine pathoge nicity. In summary, the clinical significance of the p.Glu32215Lys variant is un certain. ACMG/AMP Criteria applied: PP3.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725378 SCV000336471 uncertain significance not provided 2015-10-20 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765848 SCV000897244 uncertain significance Usher syndrome, type 2C; Febrile seizures, familial, 4 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000725378 SCV001225455 uncertain significance not provided 2019-12-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 3215 of the ADGRV1 protein (p.Glu3215Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs199499672, ExAC 0.05%). This variant has not been reported in the literature in individuals with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 46406). 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: "Benign"; 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.