ClinVar Miner

Submissions for variant NM_033629.6(TREX1):c.52G>A (p.Asp18Asn)

dbSNP: rs121908117
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000323773 SCV000329899 pathogenic not provided 2023-08-21 criteria provided, single submitter clinical testing Published functional studies demonstrate a dominant-negative effect as variant protein forms heterodimers with wild type that are deficient at degrading double-stranded DNA and inhibit double-stranded DNA degradation activity of the TREX1 wild type enzyme (Lehtinen et al., 2008; Lee-Kirsch et al., 2007); Not observed at significant frequency in large population cohorts (gnomAD); 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: 22071149, 23989343, 21808053, 24183309, 17440703, 27943079, 30685859, 18805785, 22829693, 20799324)
Labcorp Genetics (formerly Invitae), Labcorp RCV000819829 SCV000960511 pathogenic Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations 2023-03-01 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with Aicardi-Goutieres syndrome (PMID: 17440703, 20799324, 22829693, 23989343). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4185). 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. Experimental studies have shown that this missense change affects TREX1 function (PMID: 17440703, 18805785, 20871604, 25848017). For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 18 of the TREX1 protein (p.Asp18Asn).
OMIM RCV001804150 SCV000024576 pathogenic Chilblain lupus 2011-09-16 no assertion criteria provided literature only
OMIM RCV000004405 SCV000024577 pathogenic Aicardi-Goutieres syndrome 1, autosomal dominant 2011-09-16 no assertion criteria provided literature only
GeneReviews RCV000114329 SCV000147896 not provided Aicardi-Goutieres syndrome 1 no assertion provided literature only

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