Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000246351 | SCV000319897 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2015-07-21 | criteria provided, single submitter | clinical testing | The p.T204I variant (also known as c.611C>T), located in coding exon 4 of the TGFBR1 gene, results from a C to T substitution at nucleotide position 611. The threonine at codon 204 is replaced by isoleucine, an amino acid with similar properties. This variant was reported in one patient with medial fibroplasia and multi-vessel dissections (Poloskey et al.Vasc Med. 2012;17(6):371-8). 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. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since clinical data on this variant is limited at this time, its clinical significance is unclear. |
| Labcorp Genetics |
RCV000246351 | SCV000658853 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-05-07 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 204 of the TGFBR1 protein (p.Thr204Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with aortic dissections (PMID: 23064905; Invitae). ClinVar contains an entry for this variant (Variation ID: 264166). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TGFBR1 protein function. 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. |
| Gene |
RCV001582900 | SCV001820708 | uncertain significance | not provided | 2021-03-02 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 264166; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 7774578, 23064905) |
| All of Us Research Program, |
RCV003995712 | SCV004843033 | uncertain significance | Loeys-Dietz syndrome | 2023-11-30 | criteria provided, single submitter | clinical testing |