ClinVar Miner

Submissions for variant NM_033629.6(TREX1):c.294dup (p.Cys99fs) (rs760594164)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000375716 SCV000445020 likely benign TREX1-Related Disorders 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000806372 SCV000946366 pathogenic Aicardi Goutieres syndrome 1; Vasculopathy, retinal, with cerebral leukodystrophy; Chilblain Lupus 2018-10-06 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the TREX1 gene (p.Cys99Metfs*3). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 216 amino acids of the TREX1 protein. This variant is present in population databases (rs760594164, ExAC 0.1%). This variant has been observed in homozygous and compound heterozygous individuals affected with Aicardi Goutières syndrome (PMID: 24183309, 25582466). It has also been observed in the heterozygous state in a family affected with retinal vasculopathy with cerebral leukodystrophy (RVCL); however, in that family a homozygous variant in the NOTCH3 gene was found to segregate with the disease (PMID: 23602593). This variant is also known as c.294dup and c.294_295insA in the literature. ClinVar contains an entry for this variant (Variation ID: 225499). This variant disrupts the C-terminus of the TREX1 protein. Other variant(s) that disrupt this region (p.Val235Glyfs*6) have been determined to be pathogenic (PMID: 17660820, 27604306). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000490271 SCV000267538 pathogenic Aicardi Goutieres syndrome 1 2016-03-18 criteria provided, single submitter reference population

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