ClinVar Miner

Submissions for variant NM_003242.6(TGFBR2):c.1063G>A (p.Ala355Thr)

gnomAD frequency: 0.00002  dbSNP: rs104893813
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000426608 SCV000536524 uncertain significance not provided 2021-03-24 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; This variant is associated with the following publications: (PMID: 33195419, 31769227)
Invitae RCV001368997 SCV001565423 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-01-23 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 355 of the TGFBR2 protein (p.Ala355Thr). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TGFBR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 393155). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TGFBR2 protein function. This variant disrupts the p.Ala355 amino acid residue in TGFBR2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15731757). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
AiLife Diagnostics, AiLife Diagnostics RCV000426608 SCV002502121 uncertain significance not provided 2022-02-25 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV002289581 SCV002581802 uncertain significance Loeys-Dietz syndrome 2 2022-08-22 criteria provided, single submitter clinical testing

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