Submissions for variant NM_003242.6(TGFBR2):c.188A>G (p.Asn63Ser)

dbSNP: rs1432089303

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001182544	SCV001348017	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-12-05	criteria provided, single submitter	clinical testing	Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the extracellular domain of the TGFBR2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/276802 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Ambry Genetics	RCV001182544	SCV002719405	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2016-01-25	criteria provided, single submitter	clinical testing	The p.N63S variant (also known as c.188A>G), located in coding exon 2 of the TGFBR2 gene, results from an A to G substitution at nucleotide position 188. The asparagine at codon 63 is replaced by serine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is well conserved in available vertebrate species; however, serine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV004033077	SCV005016430	uncertain risk allele	Diabetic retinopathy		criteria provided, single submitter	research	Potent mutations in TGFBR2 gene encodes the transforming growth factor that have been associated with angiogenesis and diabetic retinopathy. More clinical studies are needed for stronger association. However, more evidence is required to confer the association of this particular variant rs1432089303 with diabetic retinopathy.