Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001585665 | SCV001811021 | likely pathogenic | not provided | 2024-08-28 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28645153, 30046113, 31752325, 30244537, 33199448, 34758253, 37298184, 34498404, deLen-Ojeda2024[paper]) |
| Labcorp Genetics |
RCV001585665 | SCV003524614 | pathogenic | not provided | 2024-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 136 of the PNPT1 protein (p.Arg136His). This variant is present in population databases (rs746356243, gnomAD 0.02%). This missense change has been observed in individual(s) with combined oxidative phosphorylation deficiency (PMID: 28645153, 30046113, 33199448). 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: 587375). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PNPT1 protein function. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002534523 | SCV003755532 | likely pathogenic | Inborn genetic diseases | 2024-11-25 | criteria provided, single submitter | clinical testing | The c.407G>A (p.R136H) alteration is located in exon 5 (coding exon 5) of the PNPT1 gene. This alteration results from a G to A substitution at nucleotide position 407, causing the arginine (R) at amino acid position 136 to be replaced by a histidine (H). Based on data from gnomAD, the A allele has an overall frequency of 0.002% (6/251096) total alleles studied. This variant has been identified in the homozygous state and/or in conjunction with other PNPT1 variant(s) in individual(s) with features consistent with PNPT1-related combined oxidative phosphorylation deficiency (Maitlainen, 2017; Pennisi, 2022; Leon-Ojeda, 2024). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. |
| OMIM | RCV000714514 | SCV000845204 | pathogenic | Combined oxidative phosphorylation defect type 13 | 2018-10-30 | no assertion criteria provided | literature only | |
| Genomics England Pilot Project, |
RCV000714514 | SCV001760091 | likely pathogenic | Combined oxidative phosphorylation defect type 13 | no assertion criteria provided | clinical testing |