Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000674945 | SCV000800361 | uncertain significance | Congenital hyperammonemia, type I | 2018-06-04 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000674945 | SCV002135421 | uncertain significance | Congenital hyperammonemia, type I | 2021-10-31 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 632 of the CPS1 protein (p.Ile632Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of carbamoyl phosphate synthetase I deficiency (PMID: 24813853). ClinVar contains an entry for this variant (Variation ID: 558644). 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 available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235342 | SCV003934802 | uncertain significance | not specified | 2023-05-09 | criteria provided, single submitter | clinical testing | Variant summary: CPS1 c.1895T>G (p.Ile632Arg) results in a non-conservative amino acid change located in the Carbamoyl-phosphate synthetase large subunit-like, ATP-binding domain (IPR005479) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250622 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1895T>G has been reported in the literature in an individual affected with Carbamoylphosphate Synthetase I Deficiency with a non-informative genotype (example: Haeberle_2011). These report(s) do not provide unequivocal conclusions about association of the variant with Carbamoylphosphate Synthetase I 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: 21120950). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |