Submissions for variant NM_003242.6(TGFBR2):c.326A>T (p.His109Leu)

dbSNP: rs1553627759

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000521998	SCV000621058	uncertain significance	not provided	2017-09-29	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the TGFBR2 gene. The H109L variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is also not observed in large population cohorts (Lek et al., 2016). The H109L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved in mammals. Nevertheless, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV004023610	SCV005016455	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 rs1553627759 with diabetic retinopathy.