ClinVar Miner

Submissions for variant NM_001875.5(CPS1):c.2945G>T (p.Gly982Val)

gnomAD frequency: 0.00001  dbSNP: rs121912595
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668782 SCV000793436 uncertain significance Congenital hyperammonemia, type I 2017-08-16 criteria provided, single submitter clinical testing
Invitae RCV000668782 SCV000817916 likely pathogenic Congenital hyperammonemia, type I 2023-09-27 criteria provided, single submitter clinical testing This variant disrupts the p.Gly982 amino acid residue in CPS1. Other variant(s) that disrupt this residue have been observed in individuals with CPS1-related conditions (PMID: 17310273, 20855223, 21120950), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CPS1 protein function. ClinVar contains an entry for this variant (Variation ID: 553356). This missense change has been observed in individuals with clinical features of carbamoyl phosphate synthetase I deficiency (PMID: 20855223, 21120950; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 982 of the CPS1 protein (p.Gly982Val).
Ambry Genetics RCV002531211 SCV003601800 uncertain significance Inborn genetic diseases 2022-05-09 criteria provided, single submitter clinical testing The c.2945G>T (p.G982V) alteration is located in exon 24 (coding exon 24) of the CPS1 gene. This alteration results from a G to T substitution at nucleotide position 2945, causing the glycine (G) at amino acid position 982 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000668782 SCV001453726 uncertain significance Congenital hyperammonemia, type I 2020-09-16 no assertion criteria provided clinical testing

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