Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000529677 | SCV000659347 | pathogenic | Congenital hyperammonemia, type I | 2023-05-11 | criteria provided, single submitter | clinical testing | This variant is also known as 426ins6 or c.434insGAATGG. For these reasons, this variant has been classified as Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 477854). This variant has been observed in individual(s) with carbamoyl phosphate synthetase I deficiency and/or clinical features of CPS1-related conditions (PMID: 16737834, 31392117; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant, c.306_311dup, results in the insertion of 2 amino acid(s) of the CPS1 protein (p.Asn103_Gly104dup), but otherwise preserves the integrity of the reading frame. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000529677 | SCV002500303 | likely pathogenic | Congenital hyperammonemia, type I | 2022-03-10 | criteria provided, single submitter | clinical testing | Variant summary: CPS1 c.306_311dupGAATGG (p.Asn103_Gly104dup) results in an in-frame duplication that is predicted to duplicate two amino acids into the encoded protein. The variant allele was found at a frequency of 4e-06 in 251292 control chromosomes (gnomAD). c.306_311dupGAATGG has been reported in the literature in compound heterozygous and homozygous individuals affected with Carbamoylphosphate Synthetase I Deficiency (Summar_1998, Eeds_2006, Celik_2019). 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. One ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV000529677 | SCV003835510 | likely pathogenic | Congenital hyperammonemia, type I | 2022-09-12 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003470799 | SCV004214501 | likely pathogenic | Pulmonary hypertension, neonatal, susceptibility to | 2023-09-01 | criteria provided, single submitter | clinical testing |