ClinVar Miner

Submissions for variant NM_000284.4(PDHA1):c.999A>C (p.Glu333Asp) (rs2228067)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel,ClinGen RCV001526401 SCV001736733 benign Pyruvate dehydrogenase complex deficiency 2021-05-06 reviewed by expert panel curation The allele frequency of the c.999A>C variant in the PDHA1 gene is 0.044% in gnomAD, including 25 hemizygotes. This allele frequency, and the frequency with which it is seen in hemizygotes in the general population are high enough to be classified as benign based on thresholds defined by the ClinGen PDHA1 Variant Curation Expert Panel (>0.0092%- BS1; gnomAD >16 hemizygotes- BS2). In silico predictors provide a conflicting score (REVEL score 0.509). In summary, this variant meets criteria to be classified as benign for PDHA1- related pyruvate dehydrogenase deficiency in an X-linked manner. PDHA1-specific ACMG/AMP criteria applied: (BS1, BS2). This was reviewed with the PDHA1 expert panel on 4/6/2021 and approved on 4/6/2021.
GeneDx RCV000434853 SCV000514089 benign not specified 2015-06-03 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000718338 SCV000849200 benign History of neurodevelopmental disorder 2017-03-31 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Invitae RCV000883866 SCV001027203 benign Pyruvate dehydrogenase E1-alpha deficiency 2020-12-05 criteria provided, single submitter clinical testing

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