Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000083536 | SCV000330994 | pathogenic | not provided | 2015-11-03 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000011747 | SCV000825697 | pathogenic | Ornithine carbamoyltransferase deficiency | 2022-11-01 | criteria provided, single submitter | clinical testing | This missense change has been observed in individuals with ornithine transcarbamylase (OTC) deficiency (PMID: 1721894, 9286441, 9427144, 27070778). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 225 of the OTC protein (p.Pro225Leu). ClinVar contains an entry for this variant (Variation ID: 11000). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro225 amino acid residue in OTC. Other variant(s) that disrupt this residue have been observed in individuals with OTC-related conditions (PMID: 9427144, 10946359, 19669271), which suggests that this may be a clinically significant amino acid residue. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt OTC protein function. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000011747 | SCV001364018 | pathogenic | Ornithine carbamoyltransferase deficiency | 2019-08-29 | criteria provided, single submitter | clinical testing | Variant summary: OTC c.674C>T (p.Pro225Leu) results in a non-conservative amino acid change located in the Aspartate/ornithine carbamoyltransferase, Asp/Orn-binding domain (IPR006131) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 182904 control chromosomes (gnomAD). The variant, c.674C>T, has been reported in the literature in multiple individuals affected with Ornithine Transcarbamylase Deficiency (OTCD) (Hentzen_1991, Garcia-Perez_1997, Matsuda_1997, McCullough_2000, Bijarnia-Mahay_2018). Hentzen_1991 reported this variant to segregate with OTCD in one family. These data indicate that the variant is very likely to be associated with disease. Several publications also reported (near) undetectable residual enzyme activities from patient samples (Hentzen_1991, Garcia-Perez_1997, Matsuda_1997, McCullough_2000). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic (1x) or pathogenic (2x). Based on the evidence outlined above, the variant was classified as pathogenic. |
Genome- |
RCV000011747 | SCV002033227 | pathogenic | Ornithine carbamoyltransferase deficiency | 2021-11-07 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000011747 | SCV000031979 | pathogenic | Ornithine carbamoyltransferase deficiency | 1991-12-01 | no assertion criteria provided | literature only | |
Gen |
RCV000083536 | SCV000115622 | pathogenic | not provided | no assertion criteria provided | not provided | Converted during submission to Pathogenic. | |
Genomic Research Center, |
RCV000011747 | SCV000268692 | likely pathogenic | Ornithine carbamoyltransferase deficiency | 2016-05-09 | no assertion criteria provided | clinical testing |