Submissions for variant NM_003242.6(TGFBR2):c.310C>T (p.Pro104Ser)

dbSNP: rs193922665

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030550	SCV000053221	likely pathogenic	Loeys-Dietz syndrome	2011-08-18	criteria provided, single submitter	curation	Converted during submission to Likely pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV001179055	SCV001343636	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-02-02	criteria provided, single submitter	clinical testing	This missense variant replaces proline with serine at codon 104 of the TGFBR2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). 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 been identified in 3/251060 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.
AiLife Diagnostics, AiLife Diagnostics	RCV002223764	SCV002501903	uncertain significance	not provided	2021-08-19	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001179055	SCV003783261	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-02-04	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 performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) did not meet the statistical confidence thresholds required to predict the impact of this variant on TGFBR2 function. ClinVar contains an entry for this variant (Variation ID: 36868). This variant has not been reported in the literature in individuals affected with TGFBR2-related conditions. This variant is present in population databases (rs193922665, gnomAD 0.006%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 104 of the TGFBR2 protein (p.Pro104Ser).
All of Us Research Program, National Institutes of Health	RCV003996147	SCV004839158	uncertain significance	Loeys-Dietz syndrome 2	2023-03-09	criteria provided, single submitter	clinical testing	This missense variant replaces proline with serine at codon 104 of the TGFBR2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. 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 3/251060 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.
GeneDx	RCV002223764	SCV005079358	uncertain significance	not provided	2023-09-13	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge