ClinVar Miner

Submissions for variant NM_003242.6(TGFBR2):c.1490G>A (p.Arg497Gln)

dbSNP: rs200958264
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001568524 SCV001792410 uncertain significance not provided 2021-03-11 criteria provided, single submitter clinical testing Not observed at a significant frequency 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 a patient with an ascending aortic aneurysm in published literature (Overwater et al., 2018); please note that this variant is referred to as, c.1565G>A, p.Arg522Gln, by Overwater et al. using alternate nomenclature; This variant is associated with the following publications: (PMID: 29907982)
CeGaT Center for Human Genetics Tuebingen RCV001568524 SCV002496794 uncertain significance not provided 2022-03-01 criteria provided, single submitter clinical testing TGFBR2: PP3
Invitae RCV003528315 SCV004282522 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-01-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 497 of the TGFBR2 protein (p.Arg497Gln). This variant is present in population databases (rs200958264, gnomAD 0.007%). This missense change has been observed in individual(s) with clinical features of TGFBR2-related conditions (PMID: 29907982). This variant is also known as c.1565G>A, p.Arg522Gln. ClinVar contains an entry for this variant (Variation ID: 1202728). 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 with a positive predictive value of 95%. 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.
Molecular Genetics Lab, CHRU Brest RCV003883180 SCV004697647 likely pathogenic Loeys-Dietz syndrome 2; Malignant tumor of esophagus; Colorectal cancer, hereditary nonpolyposis, type 6 criteria provided, single submitter clinical testing

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