ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.12542C>T (p.Pro4181Leu) (rs200957385)

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
GeneDx RCV000497527 SCV000590064 uncertain significance not provided 2017-06-05 criteria provided, single submitter clinical testing The P4181L variant in the ADGRV1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P4181L variant is observed in 3/14198 (0.021%) alleles from individuals of South Asian background, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P4181L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P4181L as a variant of uncertain significance.
Invitae RCV000497527 SCV001237258 uncertain significance not provided 2019-10-31 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 4181 of the ADGRV1 protein (p.Pro4181Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs200957385, ExAC 0.02%). This variant has been observed in individual(s) with cardiac conduction disorder in epilepsy (PMID: 29261713). ClinVar contains an entry for this variant (Variation ID: 432348). 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: "Tolerated"; PolyPhen-2: "Possibly 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.
Illumina Clinical Services Laboratory,Illumina RCV001157421 SCV001318989 uncertain significance Usher syndrome, type 2C 2018-01-13 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, Partners HealthCare Personalized Medicine RCV001195218 SCV001365525 uncertain significance not specified 2019-11-26 criteria provided, single submitter clinical testing The p.Pro4181Leu variant in ADGRV1 has not been previously reported in individuals with hearing loss but has been identified in 0.01% (6/30336) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant has also been reported in ClinVar (Variation ID 432348). 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: PM2_Supporting.

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.