Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000478228 | SCV000574326 | likely pathogenic | not provided | 2017-12-29 | criteria provided, single submitter | clinical testing | A variant that is likely pathogenic has been identified in the TSC2 gene. The H1620L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The H1620L variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The H1620L 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 conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, other missense variants at the same codon (H1620Y/H1620R) and in nearby residues have been reported in association with TSC (Niida et al., 1996, Hoogeveen-Westerveld et al., 2013, 2009; Stenson et al., 2014; TSC2 LOVD), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |