Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000673871 | SCV000799123 | uncertain significance | Congenital hyperammonemia, type I | 2018-04-11 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000673871 | SCV001416102 | uncertain significance | Congenital hyperammonemia, type I | 2022-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 401 of the CPS1 protein (p.Gly401Arg). This variant is present in population databases (rs760895692, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of carbamoyl phosphate synthetase 1 deficiency (PMID: 22575620, 24813853, 32718099, 33489762). ClinVar contains an entry for this variant (Variation ID: 557698). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV001267424 | SCV001445605 | uncertain significance | Inborn genetic diseases | 2018-01-26 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003317334 | SCV004020854 | uncertain significance | not specified | 2023-06-14 | criteria provided, single submitter | clinical testing | Variant summary: CPS1 c.1201G>C (p.Gly401Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 250054 control chromosomes (gnomAD v2.1, Exomes dataset). c.1201G>C has been reported in the literature in several compound heterozygous individuals affected with Carbamoylphosphate Synthetase I Deficiency (e.g., Haberle_2011, Kretz_2012, deCastro_2020, Kumar_2021, Serrano_2010, Barbosa-Gouveia_2021). However, in several affected individuals the variant was identified in cis with variant c.2810T>A (p.Ile937Asn; e.g., Diez-Fernandez_2014, Makris_2021, Toquet_2021), although the variant was confirmed in trans with the same p.Ile937Asn variant in at least one affected compound heterozygote (e.g., deCastro_2020, Barbosa-Gouveia_2021). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 34440436, 24813853, 21120950, 22575620, 33489762, 33309754, 34014557, 32718099, 19684305). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and all laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Baylor Genetics | RCV003465530 | SCV004214499 | likely pathogenic | Pulmonary hypertension, neonatal, susceptibility to | 2023-09-11 | criteria provided, single submitter | clinical testing |