Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000492997 | SCV000583056 | uncertain significance | not provided | 2017-05-13 | criteria provided, single submitter | clinical testing | The c.10411_10412delGAinsAG variant in the ADGRV1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.10411_10412delGAinsAG variant results in an in-frame substitution of Glutamine 471 with an Arginine residue, denoted p.E3471R. This missense substitution is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. The c.10411_10412delGAinsAG variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.10411_10412delGAinsAG as a variant of uncertain significance. |
Invitae | RCV000492997 | SCV001569568 | uncertain significance | not provided | 2022-06-20 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with arginine, which is basic and polar, at codon 3471 of the ADGRV1 protein (p.Glu3471Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 430285). 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |