ClinVar Miner

Submissions for variant NM_000284.4(PDHA1):c.937_940dup (p.Ser314fs) (rs137853251)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196049 SCV000252044 pathogenic not provided 2017-07-19 criteria provided, single submitter clinical testing The c.937_940dupAAGA variant in the PDHA1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.937_940dupAAGA variant causes a frameshift starting with codon Serine 314, changes this amino acid to a Lysine residue, and creates a premature Stop codon at position 3 of the new reading frame, denoted p.Ser314LysfsX3. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.937_940dupAAGA variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.937_940dupAAGA as a pathogenic variant.
Invitae RCV001224932 SCV001397159 pathogenic Pyruvate dehydrogenase E1-alpha deficiency 2019-07-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser314Lysfs*3) in the PDHA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PDHA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 214945). Loss-of-function variants in PDHA1 are known to be pathogenic (PMID: 10679936, 21914562). For these reasons, this variant has been classified as Pathogenic.

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