Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001219675 | SCV001391625 | uncertain significance | Hereditary hemorrhagic telangiectasia | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with valine at codon 281 of the ENG protein (p.Ile281Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs764640510, ExAC 0.01%). This missense change has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 30578397, 31400083). This variant is also known as c.A295G (p.I99V). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |