Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002233956 | SCV000754761 | pathogenic | Citrullinemia | 2023-03-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 528373). This premature translational stop signal has been observed in individual(s) with classical neonatal form of citrullinemia (PMID: 24889030). This variant is present in population databases (rs756859126, gnomAD 0.007%). 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. Loss-of-function variants in ASS1 are known to be pathogenic (PMID: 18473344, 19006241). |
| Counsyl | RCV000633522 | SCV000799753 | likely pathogenic | Citrullinemia type I | 2018-05-03 | criteria provided, single submitter | clinical testing | |
| 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. |
| Fulgent Genetics, |
RCV000633522 | SCV000893799 | pathogenic | Citrullinemia type I | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000633522 | SCV001163601 | pathogenic | Citrullinemia type I | criteria provided, single submitter | clinical testing | ||
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002233956 | SCV003934397 | pathogenic | Citrullinemia | 2023-05-23 | criteria provided, single submitter | clinical testing | Variant summary: ASS1 c.1069C>T (p.Gln357X) 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 250856 control chromosomes (gnomAD). c.1069C>T has been reported in the literature as a familial variant of a fetus at risk however this fetus did not appear to inherit the variant (Miller_2014). This report does not provide unequivocal conclusions about association of the variant with Citrullinemia Type I. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 24889030). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |