ClinVar Miner

Submissions for variant NM_003477.3(PDHX):c.1231C>T (p.Gln411Ter)

dbSNP: rs758020436
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003069742 SCV003469903 pathogenic not provided 2022-09-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln411*) in the PDHX gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 91 amino acid(s) of the PDHX protein. This variant is present in population databases (rs758020436, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with PDHX-related conditions. This variant disrupts a region of the PDHX protein in which other variant(s) (@p.Arg446*) have been determined to be pathogenic (PMID: 16904023, 25087164). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004526962 SCV005039615 pathogenic Pyruvate dehydrogenase E3-binding protein deficiency 2024-03-21 criteria provided, single submitter clinical testing Variant summary: PDHX c.1231C>T (p.Gln411X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein. Variant(s) downstream of this position have been classified as pathogenic in ClinVar (CV ID 162202). The variant allele was found at a frequency of 8e-06 in 249826 control chromosomes (gnomAD). c.1231C>T has been reported in the literature in individuals affected with Leigh syndrome (example: Lim_2022). The following publication has been ascertained in the context of this evaluation (PMID: 34716721). ClinVar contains an entry for this variant (Variation ID: 2158386). Based on the evidence outlined above, the variant was classified as pathogenic.

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