Submissions for variant NM_033629.6(TREX1):c.144del (p.Thr49fs)

dbSNP: rs748914604

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001593823	SCV001817010	likely pathogenic	not provided	2018-07-20	criteria provided, single submitter	clinical testing	Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 26 amino acids are lost and replaced with 15 incorrect amino acids [Human Gene Mutation Database / published literature] [(Stenson et al., 2014; other references)]; Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV001866193	SCV002142508	pathogenic	Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations	2023-09-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Thr49Profs*16) in the TREX1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 266 amino acid(s) of the TREX1 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1216160). This variant disrupts a region of the TREX1 protein in which other variant(s) (p.Arg164*) have been determined to be pathogenic (PMID: 16845398, 25604658). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.