ClinVar Miner

Submissions for variant NM_000284.4(PDHA1):c.422G>A (p.Arg141Gln)

dbSNP: rs794729213
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Revvity Omics, Revvity RCV000184034 SCV003824821 pathogenic Pyruvate dehydrogenase E1-alpha deficiency 2022-12-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000184034 SCV004299490 pathogenic Pyruvate dehydrogenase E1-alpha deficiency 2022-11-23 criteria provided, single submitter clinical testing 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 PDHA1 protein function. ClinVar contains an entry for this variant (Variation ID: 202188). This missense change has been observed in individual(s) with pyruvate dehydrogenase lipoic acid synthetase deficiency (PMID: 10679936). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 141 of the PDHA1 protein (p.Arg141Gln). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg141 amino acid residue in PDHA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11757583). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.
GeneDx RCV004589837 SCV005078201 pathogenic not provided 2024-07-12 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; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 10679936, 28584645)
Mendelics RCV000184034 SCV000236565 pathogenic Pyruvate dehydrogenase E1-alpha deficiency 2013-09-23 no assertion criteria provided clinical testing

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