Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001060968 | SCV001225690 | uncertain significance | Telangiectasia, hereditary hemorrhagic, type 5 | 2021-08-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with tryptophan at codon 216 of the GDF2 protein (p.Arg216Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs556004917, ExAC 0.009%). This missense change has been observed in individual(s) with GDF2-related conditions (PMID: 31727138). ClinVar contains an entry for this variant (Variation ID: 855657). 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: "Probably Damaging"; 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. |
| Ambry Genetics | RCV003380829 | SCV004091775 | likely benign | Cardiovascular phenotype | 2023-07-05 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |