Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001385552 | SCV001585444 | pathogenic | Neuronal ceroid lipofuscinosis 1 | 2023-11-06 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 181 of the PPT1 protein (p.Val181Leu). This variant is not present in population databases (gnomAD no frequency). A different variant (c.541G>T) giving rise to the same protein effect has been determined to be pathogenic (PMID: 10477428, 19302939, 21499717). This suggests that this variant is also likely to be causative of disease. ClinVar contains an entry for this variant (Variation ID: 1072746). 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 PPT1 protein function with a positive predictive value of 80%. This variant disrupts the p.Val181 amino acid residue in PPT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22387303, 23374165). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001547349 | SCV001767031 | likely pathogenic | not provided | 2021-05-03 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Baylor Genetics | RCV001385552 | SCV005052445 | likely pathogenic | Neuronal ceroid lipofuscinosis 1 | 2024-02-02 | criteria provided, single submitter | clinical testing |