Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000674961 | SCV000800378 | uncertain significance | Congenital hyperammonemia, type I | 2018-06-01 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003330896 | SCV004038006 | uncertain significance | not specified | 2023-08-02 | criteria provided, single submitter | clinical testing | Variant summary: CPS1 c.4471T>C (p.Tyr1491His) results in a conservative amino acid change located in the Methylglyoxal synthase-like domain (IPR011607) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251072 control chromosomes. c.4471T>C has been reported in the literature in an individual affected with late onset Carbamoylphosphate Synthetase I Deficiency (Summar_1998). However, the variant was detected in RNA, and no second variant was identified, making the complete genotype of this individual unclear. Therefore, this report does not provide unequivocal conclusions about association of the variant with Carbamoylphosphate Synthetase I Deficiency. At least one publication reports experimental evidence evaluating an impact on protein function (Pekkala_2010). The most pronounced variant effect results in 10%-<30% of normal Carbamoylphosphate Synthetase enzymatic activity in-vitro. The following publications have been ascertained in the context of this evaluation (PMID: 20578160, 9686343). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |