Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000189792 | SCV000243440 | uncertain significance | not provided | 2012-10-03 | criteria provided, single submitter | clinical testing | p.Ile468Leu (ATT>CTT):c.1402 A>C in exon 11 of the TPP1 gene (NM_000391.3)The Ile468Leu missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Ile468Leu in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is conservative, as both Isoleucine and Leucine are uncharged, non-polar amino acid residues. However, Ile468Leu alters a position in the tripeptidyl-peptidase 1 (TPP-1) protein that is well conserved in mammals. Several in silico models predict that Ile468Leu is benign, although one model indicates it may be damaging to protein structure/function. Therefore, based on the currently available information, it is unclear whether Ile468Leu is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). |