Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genomic Research Center, |
RCV000011620 | SCV000746768 | pathogenic | Pyruvate dehydrogenase E1-alpha deficiency | 2017-12-18 | criteria provided, single submitter | clinical testing | |
Institute of Medical Genetics and Applied Genomics, |
RCV001267918 | SCV001446428 | likely pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV002251895 | SCV002523221 | likely pathogenic | See cases | 2019-08-12 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PS4, PM2, PP2, PP3 |
Invitae | RCV000011620 | SCV004299496 | pathogenic | Pyruvate dehydrogenase E1-alpha deficiency | 2022-10-16 | 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 378 of the PDHA1 protein (p.Arg378His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with pyruvate dehydrogenase E1-alpha deficiency (PMID: 1909401, 16713755). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 10873). 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) has been performed at Invitae 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 PDHA1 protein function. This variant disrupts the p.Arg378 amino acid residue in PDHA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8962591, 20002125, 20002461, 24718837, 28639102). 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. |
OMIM | RCV000011620 | SCV000031852 | pathogenic | Pyruvate dehydrogenase E1-alpha deficiency | 1991-01-01 | no assertion criteria provided | literature only |