Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000243893 | SCV000319247 | uncertain significance | Cardiovascular phenotype | 2014-03-05 | criteria provided, single submitter | clinical testing | The p.T445N variant (also known as c.1334C>A), located in coding exon 5 of the TGFBR2 gene in a serine/threonine kinase domain, results from a C to A substitution at nucleotide position 1334. The threonine at codon 445 is replaced by asparagine, an amino acid with similar properties. This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. Based on protein sequence alignment, this amino acid position is highly conserved in most available vertebrate species except for fish. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
Invitae | RCV000687203 | SCV000814757 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2018-03-23 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces threonine with asparagine at codon 445 of the TGFBR2 protein (p.Thr445Asn). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TGFBR2-related disease. ClinVar contains an entry for this variant (Variation ID: 263822). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). |