ClinVar Miner

Submissions for variant NM_003242.6(TGFBR2):c.1121C>T (p.Pro374Leu)

dbSNP: rs1057524399
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000424003 SCV000535453 uncertain significance not provided 2023-07-27 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Invitae RCV001347717 SCV001541991 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2021-10-08 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 392222). This missense change has been observed in individual(s) with clinical features of TGFBR2-related conditions (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 374 of the TGFBR2 protein (p.Pro374Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine.
Ambry Genetics RCV001347717 SCV002747816 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2020-03-16 criteria provided, single submitter clinical testing The p.P374L variant (also known as c.1121C>T), located in coding exon 4 of the TGFBR2 gene, results from a C to T substitution at nucleotide position 1121. The proline at codon 374 is replaced by leucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. 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.

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