ClinVar Miner

Submissions for variant NM_001875.5(CPS1):c.2549G>A (p.Arg850His) (rs767694281)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000816596 SCV000957113 pathogenic Congenital hyperammonemia, type I 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 850 of the CPS1 protein (p.Arg850His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs767694281, ExAC 0.002%). This variant has been observed in individual(s) with carbamoylphosphate synthetase 1 deficiency (PMID: 15617192, 22575620, 27150549). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant has been reported to affect CPS1 protein function (PMID: 24813853). This variant disrupts the p.Arg850 amino acid residue in CPS1. Other variant(s) that disrupt this residue have been observed in individuals with CPS1-related conditions (PMID: 17310273), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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