ClinVar Miner

Submissions for variant NM_000050.4(ASS1):c.1069C>T (p.Gln357Ter) (rs756859126)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000757010 SCV000885031 likely pathogenic not provided 2017-07-30 criteria provided, single submitter clinical testing The c.1069C>T variant (rs756859126) has been previously reported in an unaffected carrier included in a study of pregnancies at risk for citrullinemia; however, the tested fetus was found not to carry any pathogenic variant and did not have biochemical findings consistent with citrullinemia (Miller 2014). Nonetheless, the c.1069C>T variant introduces an early termination codon into exon 14 (out of 16) in the ASS1 gene and is expected to result in a truncated or absent protein product. Consistent with a heterozygous carrier frequency, this variant is listed in the Genome Aggregation Database (gnomAD) browser with an overall frequency of 0.0004% (identified in 1 out of 245,770 chromosomes). Taken together, this variant is considered likely pathogenic.
Counsyl RCV000633522 SCV000799753 likely pathogenic Citrullinemia type I 2018-05-03 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000633522 SCV000893799 pathogenic Citrullinemia type I 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000633522 SCV000754761 pathogenic Citrullinemia type I 2018-11-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln357*) in the ASS1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs756859126, ExAC 0.01%). This variant has been reported in a family with a child affected with the classical neonatal form of citrullinemia (PMID: 24889030). Loss-of-function variants in ASS1 are known to be pathogenic (PMID: 18473344, 19006241). For these reasons, this variant has been classified as Pathogenic.

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