Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001045764 | SCV001209635 | pathogenic | Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ala139Valfs*21) in the TREX1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 176 amino acid(s) of the TREX1 protein. This variant is present in population databases (rs763229085, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with clinical features of autosomal recessive Aicardi Goutieres syndrome and an unspecified abnormality of the nervous system or stroke (PMID: 19344873, 26633542, 31719132). ClinVar contains an entry for this variant (Variation ID: 843202). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects TREX1 function (PMID: 29387804). This variant disrupts the C-terminus of the TREX1 protein. Other variant(s) that disrupt this region (p.Arg164*, p.Trp210*) have been observed in individuals with TREX1-related conditions (PMID: 16845398, 26938784). This suggests that this may be a clinically significant region of the protein. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001567593 | SCV001791308 | pathogenic | not provided | 2023-06-20 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a a significant decrease in enzymatic activity (McGlasson et al., 2017); Frameshift variant predicted to result in protein truncation, as the last 176 amino acids are replaced with 20 different amino acids, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); This variant is associated with the following publications: (PMID: 26633542, 31719132, 26938784, 16845398, 29387804, 30219631, 27943079) |
| Institute of Neurology, |
RCV002282434 | SCV002571717 | likely pathogenic | Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations; Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy | 2022-06-04 | no assertion criteria provided | research |