ClinVar Miner

Submissions for variant NM_003242.6(TGFBR2):c.412T>G (p.Cys138Gly)

gnomAD frequency: 0.00001  dbSNP: rs863223838
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000195915 SCV000250924 uncertain significance not provided 2023-09-29 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Invitae RCV000471319 SCV000548112 likely pathogenic Familial thoracic aortic aneurysm and aortic dissection 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 138 of the TGFBR2 protein (p.Cys138Gly). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individuals with clinical features of TGFBR2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 213915). 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%. This variant disrupts the p.Cys138 amino acid residue in TGFBR2. Other variant(s) that disrupt this residue have been observed in individuals with TGFBR2-related conditions (PMID: 21270064), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
AiLife Diagnostics, AiLife Diagnostics RCV000195915 SCV002502443 uncertain significance not provided 2022-01-28 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002478686 SCV002786091 uncertain significance Loeys-Dietz syndrome 2; Malignant tumor of esophagus; Colorectal cancer, hereditary nonpolyposis, type 6 2021-09-08 criteria provided, single submitter clinical testing
GenomeConnect, ClinGen RCV000509415 SCV000607137 not provided Congenital aneurysm of ascending aorta; Loeys-Dietz syndrome no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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