Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001041750 | SCV001205385 | pathogenic | Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations | 2023-11-07 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser82Leufs*9) in the TREX1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 233 amino acid(s) of the TREX1 protein. This variant is present in population databases (no rsID available, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with Aicardi-Goutières syndrome (PMID: 24183309). ClinVar contains an entry for this variant (Variation ID: 839889). This variant disrupts a region of the TREX1 protein in which other variant(s) (p.Cys99Metfs*3) have been determined to be pathogenic (PMID: 23602593, 24183309, 25582466). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV002489572 | SCV002793014 | likely pathogenic | Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Systemic lupus erythematosus; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations | 2022-04-22 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV003128257 | SCV003804665 | likely pathogenic | Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations | 2022-12-23 | criteria provided, single submitter | clinical testing | _x000D_ Criteria applied: PVS1_STR, PS4_MOD |
Prevention |
RCV004528350 | SCV004107086 | pathogenic | TREX1-related disorder | 2023-11-30 | criteria provided, single submitter | clinical testing | The TREX1 c.236_243dup8 variant is predicted to result in a frameshift and premature protein termination (p.Ser82Leufs*9). This variant has been reported, along with another TREX1 variant (phase unknown), in an individual with Aicardi-Goutières syndrome (Supplemental Table 10, Rice et al. 2013. PubMed ID: 24183309) and in the homozygous state in a fetus with brain malformations and cardiomegaly (Smogavec et al. 2022. PubMed ID: 34974531). Of note, this was the second pregnancy in that family with similar clinical presentations and it was not noted if the first pregnancy had genetic testing performed. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD and is interpreted as pathogenic/likely pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/839889/). Frameshift variants in TREX1 are expected to be pathogenic. This variant is interpreted as pathogenic. |
Institute of Medical Genetics, |
RCV001644908 | SCV001519071 | pathogenic | Aicardi-Goutieres syndrome 1 | 2021-03-10 | no assertion criteria provided | clinical testing |