Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000431389 | SCV000520993 | likely pathogenic | not provided | 2023-01-04 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 18676167, 30870574, 30045381) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235208 | SCV003934715 | uncertain significance | not specified | 2023-05-08 | criteria provided, single submitter | clinical testing | Variant summary: PC c.796T>G (p.Ser266Ala) results in a conservative amino acid change located in the Carbamoyl-phosphate synthetase large subunit-like, ATP-binding domain (IPR005479) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250800 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.796T>G has been reported in the literature as a compound heterozygous genotype with a second PC variant (c.2114C>A, p.Ser705*) of presumed somatic origin in one individual affected with Type C form of Pyruvate Carboxylase deficiency. The Type C (Benign Form) is reportedly characterized by normal or mildly delayed neurological development and episodic metabolic acidosis (Wang_2008). The authors postulated that the somatic mosaicsm could result in variable tissue distributions of the mutant genotype resulting in a milder phenotypic outcome. The overall Pyruvate Carboxylase activity in cultured skin Fibroblasts for this patient is reported as 1.9%. These report(s) do not provide unequivocal conclusions about association of the variant with Pyruvate Carboxylase Deficiency. To our knowledge, no variant specific experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 30045381, 30870574, 35782291, 18676167). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. One laboratory classified the variant as likely pathogenic citing overlapping evidence utilized in the context of this evaluation and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Baylor Genetics | RCV000675077 | SCV004202802 | likely pathogenic | Pyruvate carboxylase deficiency | 2023-08-12 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000675077 | SCV000800574 | uncertain significance | Pyruvate carboxylase deficiency | 2019-07-30 | no assertion criteria provided | clinical testing |