Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Pathology and Laboratory Medicine, |
RCV005365112 | SCV005918845 | likely pathogenic | Aicardi-Goutieres syndrome 1; Systemic lupus erythematosus; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations | 2023-04-17 | criteria provided, single submitter | research | |
| Labcorp Genetics |
RCV001857680 | SCV002134812 | uncertain significance | Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations | 2026-01-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 114 of the TREX1 protein (p.Arg114Cys). This variant is present in population databases (rs760838030, gnomAD 0.003%). This missense change has been observed in individual(s) with autosomal recessive Aicardi-Goutieres syndrome and/or chilblain lupus and cerebral vasculitis (PMID: 28919362, 33042144). This variant is also known as c.505C>T; p.R169C. ClinVar contains an entry for this variant (Variation ID: 209198). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Arg114 amino acid residue in TREX1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16845398, 17293595, 18805785). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Gene |
RCV001843490 | SCV002102675 | likely pathogenic | not provided | 2022-02-15 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32293470, 26633545, 21937424, 30685859, 28919362, 34670123) |
| Fulgent Genetics, |
RCV000763111 | SCV000893653 | likely pathogenic | Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Systemic lupus erythematosus; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000191136 | SCV000245545 | likely pathogenic | Aicardi-Goutieres syndrome 1 | 2014-07-15 | criteria provided, single submitter | clinical testing | Likely pathogenicity based on finding it once in our laboratory in trans with a pathogenic variant [V71fs] in an 18-year-old male with delayed development, neurologic regression, mineral deposition in the brain, adult-onset vision loss, inability to stand or walk, dystonia, abnormal teeth, maculopapular rash. This missense variant affects the same residue as another pathogenic variant reported in Aicardi-Goutieres syndrome (PMID 16845398, 18805785, 21270825, 21937424, 23881107). Father, who was heterozygous for this variant, had focal hand dystonia. |
| Prevention |
RCV004732774 | SCV005346168 | likely pathogenic | TREX1-related disorder | 2024-07-16 | no assertion criteria provided | clinical testing | The TREX1 c.340C>T variant is predicted to result in the amino acid substitution p.Arg114Cys. This variant was reported in individuals with Chilblain lupus and and cerebral vasculitis (Kisla Ekinci et al. 2017. PubMed ID: 28919362; Blue et al. 2021. PubMed ID: 34670123). Of note, another missense variant, affecting the same amino acid (p.Arg114His), has also been reported to be causative for Aicardi-Goutières syndrome (Crow et al. 2006. PubMed ID: 16845398; Al Mutairi et al. 2018. PubMed ID: 29239743; de Silva et al. 2007. PubMed ID: 17293595). This variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD. This variant is interpreted as likely pathogenic. |