ClinVar Miner

Submissions for variant NM_033629.6(TREX1):c.907A>C (p.Thr303Pro) (rs76224909)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000686683 SCV000814211 uncertain significance Aicardi Goutieres syndrome 1; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations; Chilblain lupus erythematosus 2018-01-30 criteria provided, single submitter clinical testing This sequence change replaces threonine with proline at codon 303 of the TREX1 protein (p.Thr303Pro). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and proline. This variant is present in population databases (rs76224909, ExAC 0.003%). This variant has been reported in a cohort of individuals affected with Aicardi-Goutieres syndrome (PMID: 17846997). Additionally, this variant was seen in a similar number of cases and controls in a study of TREX1 variants in ∼8370 patients with systemic lupus erythematosus and ∼7490 controls (PMID: 21270825). ClinVar contains an entry for this variant (Variation ID: 126394). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly 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.
GeneReviews RCV000114335 SCV000147904 pathogenic Aicardi Goutieres syndrome 1 2014-03-13 no assertion criteria provided literature only

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