Submissions for variant NM_003242.6(TGFBR2):c.98A>G (p.Asn33Ser)

dbSNP: rs2125404654

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001524902	SCV001734873	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-11-29	criteria provided, single submitter	clinical testing	This missense variant replaces asparagine with serine at codon 33 of the TGFBR2 protein. Computational prediction tool indicates that this variant may have a neutral impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TGFBR2-related disorders in the literature. This variant has not been identified 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001524902	SCV003474793	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-01-18	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: 1171653). This variant has not been reported in the literature in individuals affected with TGFBR2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 33 of the TGFBR2 protein (p.Asn33Ser).
All of Us Research Program, National Institutes of Health	RCV004008805	SCV004839147	uncertain significance	Loeys-Dietz syndrome 2	2023-12-18	criteria provided, single submitter	clinical testing	This missense variant replaces asparagine with serine at codon 33 of the TGFBR2 protein. Splice site prediction tools are inconclusive regarding the impact of this variant on RNA splicing. 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 not been identified 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.