Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Rady Children's Institute for Genomic Medicine, |
RCV000000236 | SCV001445903 | likely pathogenic | Prolidase deficiency | 2019-05-14 | criteria provided, single submitter | clinical testing | This variant has been previously reported as a compound heterozygous change in patients with prolidase deficiency (PMID: 8900231, 17142620), one of whom was reported to be asymptomatic (PMID: 8900231). An in vitro experiment in COS-1 cells demonstrated that this variant reduces prolidase activity to undetectable levels (PMID: 8900231). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.004% (9/245214) and thus is presumed to be rare. The c.833G>A (p.Gly278Asp) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.833G>A (p.Gly278Asp) variant is classified as Likely Pathogenic. |
| Invitae | RCV002512597 | SCV003443281 | pathogenic | not provided | 2023-11-30 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 278 of the PEPD protein (p.Gly278Asp). This variant is present in population databases (rs121917723, gnomAD 0.007%). This missense change has been observed in individual(s) with prolidase deficiency (PMID: 8900231, 17142620). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 212). 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 PEPD protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects PEPD function (PMID: 8900231). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000000236 | SCV000020380 | pathogenic | Prolidase deficiency | 1996-11-01 | no assertion criteria provided | literature only |