Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000185790 | SCV000238726 | uncertain significance | not provided | 2019-03-29 | criteria provided, single submitter | clinical testing | Previously reported in association with citrullinemia type I (Engel et al., 2009); Nucleotide substitution has no predicted effect on splicing and is not conserved across species; Alters the Kozak consensus sequence, which plays an important role in the initiation of protein translation; This variant is associated with the following publications: (PMID: 25087612, 19006241) |
Invitae | RCV002228803 | SCV000630059 | likely benign | Citrullinemia | 2023-09-08 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000541100 | SCV001328934 | uncertain significance | Citrullinemia type I | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Genome- |
RCV000541100 | SCV001737167 | uncertain significance | Citrullinemia type I | 2021-05-18 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000541100 | SCV002060122 | uncertain significance | Citrullinemia type I | 2021-10-01 | criteria provided, single submitter | clinical testing | NM_000050.4(ASS1):c.-4C>T is a 5' non-coding variant classified as a variant of uncertain significance in the context of citrullinemia type 1. c.-4C>T has been observed in a case with relevant disease (PMID: 28111830). Functional assessments of this variant are not available in the literature. c.-4C>T has been observed in population frequency databases (gnomAD: SAS 0.18%). In summary, there is insufficient evidence to classify NM_000050.4(ASS1):c.-4C>T as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230438 | SCV003928990 | uncertain significance | not specified | 2023-04-13 | criteria provided, single submitter | clinical testing | Variant summary: ASS1 c.-4C>T is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 0.00056 in 250834 control chromosomes in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in ASS1 causing Citrullinemia Type I (0.00056 vs 0.0041), allowing no conclusion about variant significance. The variant was reported in the literature without strong evidence for causality. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified as VUS (n=5), Likely Pathogenic (n=1) and Likely Benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Institute of Medical Genetics and Applied Genomics, |
RCV000185790 | SCV001447739 | likely pathogenic | not provided | 2020-10-23 | flagged submission | clinical testing | |
Natera, |
RCV000541100 | SCV002082214 | uncertain significance | Citrullinemia type I | 2021-06-21 | no assertion criteria provided | clinical testing |