Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000617084 | SCV000319897 | uncertain significance | Cardiovascular phenotype | 2015-07-21 | criteria provided, single submitter | clinical testing | Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Insufficient or conflicting evidence |
| Invitae | RCV000246351 | SCV000658853 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-06-29 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 204 of the TGFBR1 protein (p.Thr204Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with aortic dissections (PMID: 23064905, Invitae). ClinVar contains an entry for this variant (Variation ID: 264166). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C25"). 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. |