ClinVar

Description

p.Ala329Thr (GCC>ACC): c.985 G>A in exon 4 of the TGFBR2 gene (NM_003242.5)Mutations in the TGFBR2 gene have been reported association with Loeys Dietz syndrome and also have been reported in approximately 4% of patients with familial TAAD (Milewicz D et al., 2012).The A329T variant in the TGFBR2 gene has been reported previously in individuals with the clinical diagnosis of Loeys Dietz syndrome (Loeys et al., 2006; Barnett et al., 2011). The A329T 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. This substitution occurs at a position that is not conserved across species. Mutations in nearby residues (T325P, Y336N) have been reported in association with TGFRB2-related phenotype, further supporting the functional importance of this region of the protein. Furthermore, the A329T mutation was not observed inapproximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in TAAD