Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000199671 | SCV000252032 | pathogenic | not provided | 2022-06-28 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate that colonies harboring the R302C variant had no functional enzyme activity (Drakulic et al., 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27864847, 21846590, 25495354, 25525159, 26865159, 9671272, 1293379, 31658717, 31665995, 20002461, 29445841, 35261462) |
Ambry Genetics | RCV000622696 | SCV000742265 | pathogenic | Inborn genetic diseases | 2017-04-07 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000011626 | SCV000832378 | pathogenic | Pyruvate dehydrogenase E1-alpha deficiency | 2022-08-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PDHA1 function (PMID: 9671272, 21846590). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 10879). This missense change has been observed in individual(s) with pyruvate dehydrogenase deficiency (PMID: 1293379, 9671272, 20002461, 21846590, 26865159). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 302 of the PDHA1 protein (p.Arg302Cys). |
Genomic Medicine Lab, |
RCV000011626 | SCV001167627 | pathogenic | Pyruvate dehydrogenase E1-alpha deficiency | 2018-09-06 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000199671 | SCV001249123 | pathogenic | not provided | 2020-02-01 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000011626 | SCV001521302 | pathogenic | Pyruvate dehydrogenase E1-alpha deficiency | 2020-09-22 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
Revvity Omics, |
RCV000011626 | SCV002016565 | pathogenic | Pyruvate dehydrogenase E1-alpha deficiency | 2021-12-29 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003407316 | SCV004107140 | pathogenic | PDHA1-related condition | 2023-02-22 | criteria provided, single submitter | clinical testing | The PDHA1 c.1018C>T variant is predicted to result in the amino acid substitution p.Arg340Cys. This variant, also known as c.904C>T, p.Arg302Cys in the transcript NM_000284.4, has been reported to be causative for pyruvate dehydrogenase deficiency (Quintana et al. 2009. PubMed ID: 20002461; Glushakova et al. 2011. PubMed ID: 21846590; Parrini et al. 2017. PubMed ID: 27864847; Pirot et al. 2016. PubMed ID: 26865159; Stranneheim et al. 2014. PubMed ID: 25495354). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic. |
OMIM | RCV000011626 | SCV000031858 | pathogenic | Pyruvate dehydrogenase E1-alpha deficiency | 1998-01-01 | no assertion criteria provided | literature only |