ClinVar Miner

Submissions for variant NM_003242.6(TGFBR2):c.1222C>A (p.Leu408Met)

gnomAD frequency: 0.00001  dbSNP: rs770352403
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001070194 SCV001235411 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-11-05 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 408 of the TGFBR2 protein (p.Leu408Met). This variant is present in population databases (rs770352403, gnomAD 0.02%). This missense change has been observed in individual(s) with craniosynostosis (PMID: 29168297). ClinVar contains an entry for this variant (Variation ID: 863262). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt TGFBR2 function with a negative predictive value of 95%. 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.
Color Diagnostics, LLC DBA Color Health RCV001070194 SCV002053364 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-03-01 criteria provided, single submitter clinical testing This missense variant replaces leucine with methionine at codon 408 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 not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 20/282154 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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