ClinVar Miner

Submissions for variant NM_000284.4(PDHA1):c.934_940del (p.Ser312fs) (rs606231185)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000011619 SCV000954825 pathogenic Pyruvate dehydrogenase E1-alpha deficiency 2019-02-07 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the PDHA1 gene (p.Ser312Valfs*12). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 79 amino acids of the PDHA1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with pyruvate dehydrogenase deficiency, and has been shown to be de novo in one of the affected individuals (PMID: 2378353, 27144126, 8504306). This variant is also known as 7-bp deletion at nucleotide 1032, 7-bp deletion at bp 927 in the literature. ClinVar contains an entry for this variant (Variation ID: 10872). A different truncation (p.Glu358Glyfs*12) that lies downstream of this variant has been determined to be pathogenic (PMID: 1907799). This suggests that deletion of this region of the PDHA1 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001092567 SCV001249124 pathogenic not provided 2019-05-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001092567 SCV001447403 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
OMIM RCV000011619 SCV000031851 pathogenic Pyruvate dehydrogenase E1-alpha deficiency 2021-01-12 no assertion criteria provided literature only

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