ClinVar Miner

Submissions for variant NM_054012.4(ASS1):c.450_451del (p.Phe150fs) (rs786204648)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169436 SCV000220852 likely pathogenic Citrullinemia type I 2014-11-06 criteria provided, single submitter literature only
Invitae RCV000169436 SCV000630058 pathogenic Citrullinemia type I 2016-12-15 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides from exon 7 of the ASS1 mRNA (c.450_451delCT), causing a frameshift at codon 150. This creates a premature translational stop signal (p.Phe150Leufs*9) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in ASS1 are known to be pathogenic. This particular variant has been observed in individuals affected with citrullinemia type I (PMID: 19006241, Invitae). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000169436 SCV000694164 likely pathogenic Citrullinemia type I 2019-03-15 criteria provided, single submitter clinical testing Variant summary: ASS1 c.450_451delCT (p.Phe150LeufsX9) 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 (eg. p.Glu298fsX18). The variant allele was found at a frequency of 4.1e-06 in 246212 control chromosomes. c.450_451delCT has been reported in the literature in individuals affected with Citrullinemia Type I (Engel_2009, Diez-Fernandez_2017). 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. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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