Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001219039 | SCV001390959 | uncertain significance | Hereditary hemorrhagic telangiectasia | 2019-04-23 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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. 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"). This variant has been observed in an individuals with clinical features of hereditary hemorrhagic telangiectasia (HHT) (PMID: 24001356, Invitae). This sequence change replaces threonine with isoleucine at codon 274 of the ENG protein (p.Thr274Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. |