Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001063580 | SCV001228434 | uncertain significance | not provided | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 2988 of the ADGRV1 protein (p.Pro2988Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ADGRV1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003117732 | SCV003801218 | uncertain significance | not specified | 2023-01-10 | criteria provided, single submitter | clinical testing | Variant summary: ADGRV1 c.8963C>T (p.Pro2988Leu) results in a non-conservative amino acid change located in the Na-Ca exchanger/integrin-beta4 domain (IPR003644) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 249068 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.8963C>T in individuals affected with ADGRV1-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted a clinical-significance assessment for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |