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

gnomAD frequency: 0.00184  dbSNP: rs55999987

Total submissions: 12

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	2024-01-31	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	2024-01-01	criteria provided, single submitter	clinical testing	TREX1: BP4, BS2
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000082325	SCV004242526	uncertain significance	not specified	2024-02-06	criteria provided, single submitter	clinical testing
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