Submissions for variant NM_001875.5(CPS1):c.1030A>G (p.Thr344Ala)

dbSNP: rs1047883

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000116829	SCV000168021	benign	not specified	2013-07-25	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
PreventionGenetics, part of Exact Sciences	RCV000116829	SCV000308492	benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000116829	SCV000332075	benign	not specified	2015-06-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000364698	SCV000426823	benign	Congenital hyperammonemia, type I	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589181	SCV000697872	benign	not provided	2017-05-14	criteria provided, single submitter	clinical testing	Variant summary: The CPS1 c.1030A>G (p.Thr344Ala) variant located in the glutamine amidotransferase domain (via InterPro) involves the alteration of a non-conserved nucleotide and 2/3 in silico tools (MutationTaster not working at time of scoring and SNPsandGo had a low reliability index, therefore, not captured here) predict a benign outcome. However, these for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 68398/120062 control chromosomes (19535 homozygotes) at a frequency of 0.569689, which is approximately 360 times the estimated maximal expected allele frequency of a pathogenic CPS1 variant (0.0015811), suggesting this variant is likely a benign polymorphism. Furthermore, the observed frequency indicates that the varant of interest is the major allele in the general population. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as "likely benign/benign." Taken together, this variant is classified as benign.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000364698	SCV000744162	benign	Congenital hyperammonemia, type I	2017-05-31	criteria provided, single submitter	clinical testing
Invitae	RCV000364698	SCV001721452	benign	Congenital hyperammonemia, type I	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000364698	SCV001761737	benign	Congenital hyperammonemia, type I	2021-07-10	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002490791	SCV002813540	benign	Congenital hyperammonemia, type I; Pulmonary hypertension, neonatal, susceptibility to	2021-11-12	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000116829	SCV000150903	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000364698	SCV000734167	benign	Congenital hyperammonemia, type I		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000364698	SCV001463777	benign	Congenital hyperammonemia, type I	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000116829	SCV001919181	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000116829	SCV001959019	benign	not specified		no assertion criteria provided	clinical testing