ClinVar Miner

Submissions for variant NM_000284.4(PDHA1):c.934_992dup (p.Ser331delinsArgValArgValThrLeuLeuCysPheSerArgThrGlyTrpTer) (rs1602231539)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000793164 SCV000932505 pathogenic Pyruvate dehydrogenase E1-alpha deficiency 2018-07-25 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the PDHA1 gene (p.Ser331Argfs*15). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 60 amino acids of the PDHA1 protein. 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 disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. 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.

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