Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000669266 | SCV000794002 | pathogenic | Congenital hyperammonemia, type I | 2017-09-06 | criteria provided, single submitter | clinical testing | |
| 3billion | RCV000669266 | SCV002011955 | pathogenic | Congenital hyperammonemia, type I | 2021-10-02 | criteria provided, single submitter | clinical testing | Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.00002, PM2). The variant was observed in trans with a pathogenic variant (NM_001875.4: c.2339G>A) as compound heterozygous (3billion dataset, PM3). The variant has been reported as pathogenic/likely pathogenic without evidence for the classification (ClinVar ID:VCV000553751.1). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000669266 | SCV002556146 | pathogenic | Congenital hyperammonemia, type I | 2022-06-24 | criteria provided, single submitter | clinical testing | Variant summary: CPS1 c.1529delG (p.Gly510AlafsX5) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 2e-05 in 250518 control chromosomes. c.1529delG has been reported in the literature in multiple individuals affected with Carbamoylphosphate Synthetase I Deficiency in the homozygous and compound heterozygous state (example: Yamaguchi_2016). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV003465490 | SCV004216184 | pathogenic | Pulmonary hypertension, neonatal, susceptibility to | 2023-02-20 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000669266 | SCV004293065 | pathogenic | Congenital hyperammonemia, type I | 2023-09-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly510Alafs*5) in the CPS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CPS1 are known to be pathogenic (PMID: 21120950). This variant is present in population databases (rs764384490, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with carbamoyl phosphate synthetase I deficiency (PMID: 15617192). This variant is also known as 1528delG (510-514 ARQLX). ClinVar contains an entry for this variant (Variation ID: 553751). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000669266 | SCV000022685 | pathogenic | Congenital hyperammonemia, type I | 2007-01-01 | no assertion criteria provided | literature only |