Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001180059 | SCV001344911 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-04-05 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 298 of the TGFBR2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 10/250930 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV001180059 | SCV003781245 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 298 of the TGFBR2 protein (p.Asn298Ser). This variant is present in population databases (rs751587466, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TGFBR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 920960). 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) performed at Invitae indicates that this missense variant is not expected to disrupt TGFBR2 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. |
| CHEO Genetics Diagnostic Laboratory, |
RCV001180059 | SCV003838136 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-12-21 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004006619 | SCV004839199 | uncertain significance | Loeys-Dietz syndrome 2 | 2023-11-30 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 298 of the TGFBR2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 10/250930 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV001180059 | SCV005514870 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2024-11-20 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |