Submissions for variant NM_054012.4(ASS1):c.319del (p.Gln107fs)

dbSNP: rs1564903969

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002233293	SCV000824101	pathogenic	Citrullinemia	2018-02-23	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ASS1 are known to be pathogenic (PMID: 18473344, 19006241). This variant has not been reported in the literature in individuals with ASS1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln107Serfs*33) in the ASS1 gene. It is expected to result in an absent or disrupted protein product.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000695591	SCV001361256	likely pathogenic	Citrullinemia type I	2019-05-16	criteria provided, single submitter	clinical testing	Variant summary: ASS1 c.319delC (p.Gln107SerfsX33) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (c.892delG, p.Glu298fsX18; c.1030C>T, p.Arg344X). The variant was absent in 249828 control chromosomes (gnomAD). To our knowledge, no occurrence of c.319delC in individuals affected with Citrullinemia Type I and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.