ClinVar Miner

Submissions for variant NM_003242.6(TGFBR2):c.1043G>A (p.Arg348His)

gnomAD frequency: 0.00002  dbSNP: rs369450067
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498047 SCV000590142 uncertain significance not provided 2023-06-26 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Reported as a polymorphism in an individual with suspected Marfan syndrome or a related disorder; additional clinical details were not provided (Stheneur et al., 2008); This variant is associated with the following publications: (PMID: 27879313, 18781618)
Invitae RCV000809072 SCV000949211 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-03-28 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. 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 TGFBR2 protein function. ClinVar contains an entry for this variant (Variation ID: 432420). This missense change has been observed in individual(s) with clinical features of TGFBR2-related disease (PMID: 18781618). This variant is present in population databases (rs369450067, gnomAD 0.008%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 348 of the TGFBR2 protein (p.Arg348His).
Color Diagnostics, LLC DBA Color Health RCV000809072 SCV001354469 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-03-20 criteria provided, single submitter clinical testing This missense variant replaces arginine with histidine at codon 348 of the TGFBR2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual suspected with Marfan syndrome or related disorders (PMID: 18781618). This variant has been identified in 10/280264 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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