ClinVar Miner

Submissions for variant NM_001875.5(CPS1):c.1424del (p.Gly475fs)

dbSNP: rs1375157321
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001382268 SCV001580949 pathogenic Congenital hyperammonemia, type I 2024-10-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly475Alafs*2) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of carbamoyl phosphate synthetase I deficiency (PMID: 32154057). ClinVar contains an entry for this variant (Variation ID: 1070204). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003469674 SCV004216203 likely pathogenic Pulmonary hypertension, neonatal, susceptibility to 2022-06-29 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005023137 SCV005655758 pathogenic Congenital hyperammonemia, type I; Pulmonary hypertension, neonatal, susceptibility to 2024-02-28 criteria provided, single submitter clinical testing
Natera, Inc. RCV001382268 SCV002076225 pathogenic Congenital hyperammonemia, type I 2021-09-29 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004731144 SCV005335738 pathogenic CPS1-related disorder 2024-06-25 no assertion criteria provided clinical testing The CPS1 c.1424delG variant is predicted to result in a frameshift and premature protein termination (p.Gly475Alafs*2). This variant has been reported in the homozygous state in an individual with carbamoyl phosphate synthetase I deficiency (Table S2, Makris et al. 2021. PubMed ID: 33309754; Table S2, Isler et al. 2020. PubMed ID: 32154057). This variant has not been reported in a large population database, indicating this variant is rare. Frameshift variants in CPS1 are expected to be pathogenic. This variant is interpreted as pathogenic.

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