Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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syndrome and was found to occur de novo in 3 of these i ndividuals (Ki 2005, Sakai 2006, Uike 2013, Amor 2012, LMM unpublished data).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 (http://pcpgm.partners.org/LMM) based upon segregation studies and absence from controls. |
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000624184 | SCV000740528 | pathogenic | Loeys-Dietz syndrome 2 | 2015-11-30 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000805236 | SCV000945184 | pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2020-07-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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"). This variant has been observed in individual(s) with TGFBR2-related conditions (PMID: 16283890, 16835936, 22095581, 24220024, 27611364). In at least one individual the variant was observed to be de novo. This variant is also known as c.1142G>C (p.Arg381Pro) in the literature. ClinVar contains an entry for this variant (Variation ID: 177704). This variant is not present in population databases (ExAC no frequency). 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. |
Revvity Omics, |
RCV003488403 | SCV004238758 | likely pathogenic | not provided | 2023-03-10 | criteria provided, single submitter | clinical testing |