Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000413741 | SCV000491424 | likely pathogenic | not provided | 2016-02-02 | criteria provided, single submitter | clinical testing | A L362P variant that is likely pathogenic has been identified in the TSC2 gene. The L362P variant has been reported in the TSC2 LOVD database as probably pathogenic because it was identified as a de novo change in an individual with TSC and a fetus with a cardiac rhabdomyoma (TSC2 LOVD). However, additional clinical information was not provided and functional characterization of the variant was not completed. It was not observed in approximately 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. The L362P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, 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. Furthermore, a missense variant in a nearby residue (L361P) has been reported in the TSC2 LOVD in association with TSC (TSC2 LOVD). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Tuberous sclerosis database |
RCV000042395 | SCV000066185 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |