ClinVar Miner

Submissions for variant NM_004612.4(TGFBR1):c.926C>T (p.Thr309Met)

gnomAD frequency: 0.00003  dbSNP: rs200518416
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001210233 SCV001381708 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-02-24 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 309 of the TGFBR1 protein (p.Thr309Met). This variant is present in population databases (rs200518416, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with TGFBR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 940612). 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 not expected to disrupt TGFBR1 protein function. 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.
Fulgent Genetics, Fulgent Genetics RCV002484139 SCV002782986 uncertain significance Loeys-Dietz syndrome 1; Multiple self-healing squamous epithelioma 2021-11-16 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004010679 SCV004819684 uncertain significance Loeys-Dietz syndrome 2023-12-18 criteria provided, single submitter clinical testing This missense variant replaces threonine with methionine at codon 309 of the TGFBR1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with bicuspid aortic valve and thoracic aortic aneurysm (PMID: 28659821). This variant has been identified in 8/282486 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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