ClinVar Miner

Submissions for variant NM_001875.5(CPS1):c.1926del (p.Asp642fs) (rs1326644714)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523444 SCV000620289 likely pathogenic not provided 2017-09-07 criteria provided, single submitter clinical testing The c.1926delC variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.1926delC variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The deletion causes a frameshift starting with codon Aspartic Acid 642, changes this amino acid to a Glutamic Acid residue and creates a premature Stop codon at position 39 of the new reading frame, denoted p.Asp642GlufsX39. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret this variant as likely pathogenic.
Invitae RCV000690237 SCV000817917 pathogenic Congenital hyperammonemia, type I 2018-10-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp642Glufs*39) in the CPS1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another CPS1 variant in individuals affected with neonatal hyperammonemia or carbamoyl phosphate synthetase I deficiency (Invitae). ClinVar contains an entry for this variant (Variation ID: 451569). Loss-of-function variants in CPS1 are known to be pathogenic (PMID: 21120950). For these reasons, this variant has been classified as Pathogenic.

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