Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000039662 | SCV000063351 | uncertain significance | not specified | 2018-01-25 | criteria provided, single submitter | clinical testing | The p.Glu3215Lys variant in ADGRV1 has been previously reported by our laborator y in 2 individuals with hearing loss, one of whom also harbored a second ADGRV1 variant of uncertain significance (trans/cis not yet determined). The variant wa s also identified in 51/126478 European chromosomes by the Genome Aggregation Da tabase (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs199499672). However, t his frequency is not high enough to rule out a pathogenic role. Computational pr ediction tools and conservation analysis suggest that this variant may impact th e protein, though this information is not predictive enough to determine pathoge nicity. In summary, the clinical significance of the p.Glu32215Lys variant is un certain. ACMG/AMP Criteria applied: PP3. |
| EGL Genetic Diagnostics, |
RCV000725378 | SCV000336471 | uncertain significance | not provided | 2015-10-20 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000765848 | SCV000897244 | uncertain significance | Usher syndrome, type 2C; Febrile seizures, familial, 4 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000725378 | SCV001225455 | uncertain significance | not provided | 2019-12-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 3215 of the ADGRV1 protein (p.Glu3215Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs199499672, ExAC 0.05%). This variant has not been reported in the literature in individuals with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 46406). 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: "Deleterious"; PolyPhen-2: "Benign"; 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. |