ClinVar Miner

Submissions for variant NM_000284.4(PDHA1):c.1132C>T (p.Arg378Cys) (rs863224147)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000198575 SCV000252034 pathogenic not provided 2020-12-22 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); 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: 20002461, 10679936, 28639102, 27629047, 31665838, 8962591, 32445240, 33092611)
Center of Genomic medicine, Geneva,University Hospital of Geneva RCV000497402 SCV000590879 pathogenic Pyruvate dehydrogenase E1-alpha deficiency 2017-06-07 criteria provided, single submitter clinical testing This missense variant in the PDHA1 gene was identified in a female patient with developmental delay and neurological disorder.
Invitae RCV000497402 SCV001393905 pathogenic Pyruvate dehydrogenase E1-alpha deficiency 2019-06-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 378 of the PDHA1 protein (p.Arg378Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with pyruvate dehydrogenase lipoic acid synthetase deficiency and to be de novo in at least one individual (PMID: 20002461, 20002125, 24718837, 8962591, 28639102). ClinVar contains an entry for this variant (Variation ID: 214936). 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). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center RCV000497402 SCV001429428 pathogenic Pyruvate dehydrogenase E1-alpha deficiency 2018-12-20 criteria provided, single submitter clinical testing

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