Submissions for variant NM_033629.6(TREX1):c.623G>C (p.Cys208Ser)

gnomAD frequency: 0.00009  dbSNP: rs146524913

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000691299	SCV000819051	uncertain significance	Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations	2022-10-22	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 208 of the TREX1 protein (p.Cys208Ser). This variant is present in population databases (rs146524913, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TREX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 570429). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Fulgent Genetics, Fulgent Genetics	RCV002485645	SCV002787686	uncertain significance	Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Systemic lupus erythematosus; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations	2021-10-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003420227	SCV004113143	uncertain significance	TREX1-related condition	2023-06-21	criteria provided, single submitter	clinical testing	The TREX1 c.788G>C variant is predicted to result in the amino acid substitution p.Cys263Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.017% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-48508677-G-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001726303	SCV001963480	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001726303	SCV001967015	uncertain significance	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001726303	SCV002036115	uncertain significance	not provided		no assertion criteria provided	clinical testing
Institute of Neurology, Charite University of Medicine	RCV002282329	SCV002571719	likely benign	Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Inborn genetic diseases	2022-06-04	no assertion criteria provided	research