Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000606270 | SCV000713063 | likely benign | not specified | 2017-03-26 | criteria provided, single submitter | clinical testing | p.Arg2733Leu in exon 35 of GPR98: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. Of note, 2 mammals (Egyptian jerboa, domestic goat) and >10 birds have a leucine ( Leu) at this position despite high nearby amino acid conservation. Additional co mputational prediction tools do not suggest a high likelihood of impact to the p rotein. |
| Invitae | RCV001860253 | SCV002210970 | uncertain significance | not provided | 2021-08-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with leucine at codon 2733 of the ADGRV1 protein (p.Arg2733Leu). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with retinitis pigmentosa (Invitae). ClinVar contains an entry for this variant (Variation ID: 505690). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |