Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000509046 | SCV000915946 | uncertain significance | Phosphoenolpyruvate carboxykinase deficiency, cytosolic | 2018-09-07 | criteria provided, single submitter | clinical testing | The PCK1 c.134T>C (p.Ile45Thr) variant has been reported in one study and in one sibling pair from non-consanguineous parents, both in a homozygous state (Adams et al. 2014). Both the unaffected parents were heterozygous for the variant. The p.Ile45Thr variant is reported at a frequency of 0.001726 in the Ashkenazi Jewish population of the Genome Aggregation Database. PEPCK-C (cytosolic) and PEPCK-M (mitochondrial) activity was measured in frozen liver from one of the patients, who was found to have less than or equal to 10% of immuno-reactive PEPCK-C levels. Expression of the p.Ile45Thr variant protein in E.coli revealed it to be expressed as an insoluble protein largely located in inclusion bodies. The half-life of the p.Ile45Thr variant protein was two hours as compared to the 24 hour half-life of the wild type protein. The p.Ile45Thr variant did not affect mRNA stability. Based on the limited evidence, the p.Ile45Thr variant is classified as a variant of unknown significance but suspicious for pathogenicity for phosphoenolpyruvate carboxykinase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| OMIM | RCV000509046 | SCV000606822 | pathogenic | Phosphoenolpyruvate carboxykinase deficiency, cytosolic | 2017-10-05 | no assertion criteria provided | literature only |