ClinVar Miner

Submissions for variant NM_003242.6(TGFBR2):c.1067G>C (p.Arg356Pro) (rs727504292)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000154307 SCV000203967 pathogenic Loeys-Dietz syndrome 2014-08-29 criteria provided, single submitter clinical testing The Arg356Pro variant in TGFBR2 has been reported in 5 individuals with clinical features of Loeys-Dietz syndrome and was found to occur de novo in 3 of these i ndividuals (Ki 2005, Sakai 2006, Uike 2013, Amor 2012, LMM unpublished data). Th is variant was absent from large population studies. Computational prediction to ols and conservation analysis suggest that the Arg356Pro variant may impact the protein, though this information is not predictive enough to determine pathogeni city. In summary, this variant meets our criteria to be classified as pathogenic ( based upon segregation studies and absence from controls.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000624184 SCV000740528 pathogenic Loeys-Dietz syndrome 2 2015-11-30 criteria provided, single submitter clinical testing
Invitae RCV000805236 SCV000945184 pathogenic Thoracic aortic aneurysm and aortic dissection 2018-10-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 356 of the TGFBR2 protein (p.Arg356Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with Loeys-Dietz syndrome or with clinical features of this condition, in which some observations have been reported to be de novo (PMID: 16283890, 16835936, 22095581, 24220024, 27611364). This variant is also known as c.1142G>C (p.Arg381Pro) in the literature. ClinVar contains an entry for this variant (Variation ID: 177704). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). For these reasons, this variant has been classified as Pathogenic.

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