Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000198591 | SCV000252060 | likely benign | not provided | 2021-03-03 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 21937992) |
| Fulgent Genetics, |
RCV000023731 | SCV000894620 | uncertain significance | Pyruvate dehydrogenase E3-binding protein deficiency | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000198591 | SCV003250418 | uncertain significance | not provided | 2022-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 15 of the PDHX protein (p.Arg15His). This variant is present in population databases (rs387906998, gnomAD 0.4%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with pyruvate dehydrogenase deficiency (PMID: 21937992). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 30752). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003330399 | SCV004038958 | uncertain significance | not specified | 2023-08-10 | criteria provided, single submitter | clinical testing | Variant summary: PDHX c.44G>A (p.Arg15His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00055 in 248950 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in PDHX causing Pyruvate Dehydrogenase E3-Binding Protein Deficiency (0.00055 vs 0.0011), allowing no conclusion about variant significance. c.44G>A has been reported in the literature in a family affected with intellectual disability (example: Najmabadi_2011). This report does not provide unequivocal conclusions about association of the variant with Pyruvate Dehydrogenase E3-Binding Protein Deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 21937992). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=2) and likely benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| OMIM | RCV000023731 | SCV000045022 | pathogenic | Pyruvate dehydrogenase E3-binding protein deficiency | 2011-09-21 | no assertion criteria provided | literature only |