ClinVar Miner

Submissions for variant NM_003477.3(PDHX):c.749C>T (p.Thr250Ile) (rs146876119)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000195913 SCV000252064 uncertain significance not provided 2018-04-26 criteria provided, single submitter clinical testing p.Thr250Ile (ACA>ATA): c.749 C>T in exon 6 in the PDHX gene (NM_003477.2). The T250I variant in the PDHX gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The T250I variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The T250I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. We interpret T250I as a variant of unknown significance. The variant is found in MITONUC-MITOP panel(s).
Illumina Clinical Services Laboratory,Illumina RCV000340991 SCV000371625 uncertain significance Pyruvate dehydrogenase E3-binding protein deficiency 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000195913 SCV001121776 benign not provided 2019-12-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000195913 SCV001148227 uncertain significance not provided 2017-08-01 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.