Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000799279 | SCV000938934 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-07-05 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 303 of the TGFBR2 protein (p.Asn303His). This variant is present in population databases (rs773932892, gnomAD 0.0009%). 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: 645234). 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 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, |
RCV000799279 | SCV002042885 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-06-08 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000799279 | SCV002684669 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-08-07 | criteria provided, single submitter | clinical testing | The p.N303H variant (also known as c.907A>C), located in coding exon 4 of the TGFBR2 gene, results from an A to C substitution at nucleotide position 907. The asparagine at codon 303 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003413599 | SCV004114542 | uncertain significance | TGFBR2-related condition | 2022-12-31 | criteria provided, single submitter | clinical testing | The TGFBR2 c.907A>C variant is predicted to result in the amino acid substitution p.Asn303His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-30713582-A-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |