ClinVar Miner

Submissions for variant NM_033629.6(TREX1):c.340C>T (p.Arg114Cys)

gnomAD frequency: 0.00001  dbSNP: rs760838030
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
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.
Fulgent Genetics, 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
GeneDx 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)
Invitae RCV001857680 SCV002134812 uncertain significance Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations 2022-09-05 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 chilblain lupus and cerebral vasculitis (PMID: 28919362). ClinVar contains an entry for this variant (Variation ID: 209198). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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.

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