Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000484861 | SCV000566499 | pathogenic | not provided | 2021-02-17 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30870574, 19306334, 18676167, 25058219) |
| Labcorp Genetics |
RCV000020384 | SCV001390161 | pathogenic | Pyruvate carboxylase deficiency | 2023-07-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PC protein function. ClinVar contains an entry for this variant (Variation ID: 21222). This missense change has been observed in individual(s) with pyruvate carboxylase deficiency (PMID: 18676167, 19306334). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs113994145, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 631 of the PC protein (p.Arg631Gln). |
| Baylor Genetics | RCV000020384 | SCV004202807 | likely pathogenic | Pyruvate carboxylase deficiency | 2024-03-28 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000020384 | SCV004803246 | likely pathogenic | Pyruvate carboxylase deficiency | 2024-01-12 | criteria provided, single submitter | clinical testing | Variant summary: PC c.1892G>A (p.Arg631Gln) results in a conservative amino acid change located in the Pyruvate carboxyltransferase domain (IPR000891) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250902 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1892G>A has been reported in the literature in individuals affected with Pyruvate Carboxylase Deficiency (e.g., Monnot_2009, Wang_2008, Taylor_2014, Habarou_2015, Laura-Duque-Lasio_2023). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 28649521, 19306334, 25058219, 18676167, 37207470). ClinVar contains an entry for this variant (Variation ID: 21222). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Counsyl | RCV000020384 | SCV001132450 | likely pathogenic | Pyruvate carboxylase deficiency | 2017-04-07 | no assertion criteria provided | clinical testing |