Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000413915 | SCV000490989 | likely pathogenic | not provided | 2015-05-22 | criteria provided, single submitter | clinical testing | The L525R missense change has not been published as a pathogenic variant nor has it been reported as a benign polymorphism to our knowledge. 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 L525R 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 highly conserved across species. A different amino acid substitution at the same position (L525P) and missense variants in nearby residues (W531C, G534R) have been reported in the Human Gene Mutation Database in association with disorders in the Noonan syndrome spectrum (Stenson et al., 2009), supporting the functional importance of this region of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded. |
Department Of Pathology & Laboratory Medicine, |
RCV003448979 | SCV004176810 | likely pathogenic | Malignant lymphoma, large B-cell, diffuse | 2023-12-04 | no assertion criteria provided | clinical testing | Post-initial therapy specimen. |