Submissions for variant NM_054012.4(ASS1):c.1030C>T (p.Arg344Ter)

gnomAD frequency: 0.00001  dbSNP: rs786204537

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169239	SCV000220513	likely pathogenic	Citrullinemia type I	2014-07-15	criteria provided, single submitter	literature only
Invitae	RCV002228610	SCV000954094	pathogenic	Citrullinemia	2023-11-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg344*) in the ASS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ASS1 are known to be pathogenic (PMID: 18473344, 19006241). This variant is present in population databases (rs786204537, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with citrullinemia (PMID: 28111830). ClinVar contains an entry for this variant (Variation ID: 188885). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV000169239	SCV001163600	pathogenic	Citrullinemia type I	2024-02-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000169239	SCV001363611	pathogenic	Citrullinemia type I	2019-04-25	criteria provided, single submitter	clinical testing	Variant summary: ASS1 c.1030C>T (p.Arg344X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 251214 control chromosomes (gnomAD). c.1030C>T has been reported in the literature in compound heterozygote and homozygote individuals affected with Citrullinemia Type I (Diez-Fernandez_2017, Engel_2009). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV000169239	SCV005052013	pathogenic	Citrullinemia type I	2024-02-01	criteria provided, single submitter	curation
Natera, Inc.	RCV000169239	SCV001453092	pathogenic	Citrullinemia type I	2020-09-16	no assertion criteria provided	clinical testing