ClinVar Miner

Submissions for variant NM_033629.6(TREX1):c.797A>G (p.Glu266Gly)

gnomAD frequency: 0.00175  dbSNP: rs55999987
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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000431072 SCV000114288 uncertain significance not provided 2013-09-24 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000262094 SCV000445035 likely benign Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000300719 SCV000445036 likely benign Aicardi Goutieres syndrome 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000082325 SCV000490863 uncertain significance not specified 2016-09-28 criteria provided, single submitter clinical testing The E266G variant has not been published in association with Aicardi-Goutieres syndrome. However, the E266G variant has been published in association with systemic lupus erythematosus (SLE) (Namjou et al., 2011; Lee-Kirsch et al., 2007). Namjou et al., reports identifying the E266G variant in 5 patients of African decent diagnosed with SLE but not in ethnically matched controls (Namjou et al., 2011). This variant was also identified identified in members of the cohort of European decent but also within ethnically matched controls (Namjou et al., 2011). The NHLBI Exome Sequencing Project reports E266G was observed in 33/8600 (0.38%) alleles from individuals of European background, and the 1000 Genomes Project Consortium reports E266G was observed in 1/978 (0.1%) alleles from individuals of South Asian background. The E266G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000431072 SCV000510785 uncertain significance not provided 2017-02-09 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001082165 SCV000765744 benign Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations 2025-02-03 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000431072 SCV000844510 uncertain significance not provided 2018-04-23 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000431072 SCV002496827 likely benign not provided 2025-03-01 criteria provided, single submitter clinical testing TREX1: BP4, BS2
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000082325 SCV004242526 uncertain significance not specified 2025-03-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000082325 SCV005883284 uncertain significance not specified 2024-12-17 criteria provided, single submitter clinical testing Variant summary: TREX1 c.797A>G (p.Glu266Gly) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0017 in 251436 control chromosomes, predominantly at a frequency of 0.0029 within the Non-Finnish European subpopulation in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in TREX1 causing Aicardi-Goutieres Syndrome 1-AR (0.0017 vs 0.011), allowing no conclusion about variant significance. c.797A>G has been reported in the literature in two unspecified individuals without primary infomration (Dineiro_2020). These report(s) do not provide unequivocal conclusions about association of the variant with Aicardi-Goutieres Syndrome 1-AR. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 32483926). ClinVar contains an entry for this variant (Variation ID: 96242). Based on the evidence outlined above, the variant was classified as uncertain significance.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV005394348 SCV006053114 likely benign Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Systemic lupus erythematosus; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations 2020-06-01 criteria provided, single submitter research
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000082325 SCV001927336 benign not specified no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000431072 SCV002035847 likely benign not provided no assertion criteria provided clinical testing
Institute of Neurology, Charite University of Medicine RCV002281915 SCV002571720 likely benign Aicardi-Goutieres syndrome 1; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations 2022-06-04 no assertion criteria provided research
PreventionGenetics, part of Exact Sciences RCV004732658 SCV005351960 likely benign TREX1-related disorder 2024-08-09 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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