Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000378411 | SCV000329900 | likely pathogenic | not provided | 2018-04-23 | criteria provided, single submitter | clinical testing | The R164X variant in the TREX1 gene has been reported previously in the homozygousstate in an individual with Aicardi-Goutieres syndrome; this individual's consanguineous unaffected parents were both found to be heterozygous carriers of the variant (Crow et al., 2006). This variant is predicted to cause loss of normal protein function through protein truncation. The R164X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R164X as a likely pathogenic variant. |
Invitae | RCV001384591 | SCV001584140 | pathogenic | Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg164*) in the TREX1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 151 amino acid(s) of the TREX1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with autosomal recessive Aicardi-Goutieres syndrome (PMID: 16845398, 25604658; Invitae). It is commonly reported in individuals of Cree Native American ancestry (PMID: 25604658). ClinVar contains an entry for this variant (Variation ID: 4180). For these reasons, this variant has been classified as Pathogenic. |
Prevention |
RCV003415649 | SCV004115190 | pathogenic | TREX1-related condition | 2022-11-11 | criteria provided, single submitter | clinical testing | The TREX1 c.655C>T variant is predicted to result in premature protein termination (p.Arg219*). This variant was reported in the homozygous state in patients with Aicardi-Goutières syndrome and it is found to be a recurrent founder mutation in TREX1 observed in individuals of Cree ancestry (reported as c.490C>T, p.Arg164* in Crow YJ et al 2006. PubMed ID: 16845398; Crow YJ et al 1993. PubMed ID: 20301648; supple Table 1 in Crow YJ et al 2015. PubMed ID: 25604658). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in TREX1 are expected to be pathogenic. This variant is interpreted as pathogenic. |
OMIM | RCV000004398 | SCV000024570 | pathogenic | Aicardi-Goutieres syndrome 1 | 2006-08-01 | no assertion criteria provided | literature only | |
Gene |
RCV000004398 | SCV000147894 | not provided | Aicardi-Goutieres syndrome 1 | no assertion provided | literature only |