Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000150784 | SCV000198285 | likely benign | not specified | 2013-06-08 | criteria provided, single submitter | clinical testing | Ile4572Phe in exon 68 of GPR98: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including mammals. Of n ote, mouse, rat, kangaroo rat, guinea pig and other distance species have a phen ylalanine at this position despite high nearby amino acid conservation. In addit ion, computational analyses (PolyPhen2, SIFT, AlignGVGD) do not suggest a high l ikelihood of impact to the protein. |
| Invitae | RCV001850051 | SCV002132068 | uncertain significance | not provided | 2021-08-14 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with phenylalanine at codon 4572 of the ADGRV1 protein (p.Ile4572Phe). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and phenylalanine. This variant is present in population databases (rs727503082, ExAC 0.002%). 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: 163615). 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 phenylalanine 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. |