Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000558562 | SCV000628904 | uncertain significance | not provided | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 497 of the TPP1 protein (p.Arg497Cys). This variant is present in population databases (rs377700188, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with TPP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 457941). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TPP1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Gene |
RCV000558562 | SCV001993030 | uncertain significance | not provided | 2019-01-29 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
Natera, |
RCV001834753 | SCV002094801 | uncertain significance | Neuronal ceroid lipofuscinosis 2 | 2021-02-22 | no assertion criteria provided | clinical testing |