ClinVar

Description

The patient had genetic testing with the Ambry Genetics laboratory. The test included sequencing of 22 genes associated with aneurysms and dissections and related conditions: ACTA2, COL3A1, COL5A2, FBN1, FBN2, MED12, MYH11, MYLK, NOTCH1, PLOD1, PRKG1, SKI, SLC2A10, SMAD3, TGFB2, TGFBR1 and TGFBR2 (sequencing and deletion/duplication); CBS, COL5A1, FLNA, SMAD4 and TGFB3 (sequencing only). Results show that no disease-causing variants were found. p.L48R (c.143T>G) in the TGFBR2 gene (NM_003238) The lab classifies this variant as a variant of unknown significance. Given a lack of case data we consider this variant of unknown significance and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). This variant is novel and has not been reported in the literature before. In silico analysis with PolyPhen-2 predicts the variant to be probably damaging. The leucine at codon 48 is conserved across species, as are neighboring amino acids. No other pathogenic variants are listed in Clinvar near this position. There is no variation at codon 48 listed in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/), which currently includes variant calls on ~64,000 individuals of European, African, Latino and Asian descent (as of August 3, 2016).