Submissions for variant NM_033629.6(TREX1):c.703dup (p.Val235fs)

dbSNP: rs1553820434

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000519088	SCV000617737	pathogenic	not provided	2023-07-20	criteria provided, single submitter	clinical testing	Published functional studies demonstrate the c.703dupG variant results in the loss of a protein localization signal (Richards et al., 2007); Frameshift variant predicted to result in protein truncation, as the last 80 amino acids are replaced with 5 different amino acids, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 3174024, 1821204, 27604306, 28013302, 29386495, 29718010, 33254089, 33516249, 18805785, 17660820, 25213617)
Invitae	RCV000795266	SCV000934715	pathogenic	Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations	2023-12-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val235Glyfs*6) in the TREX1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 80 amino acid(s) of the TREX1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with retinal vasculopathy with cerebral leukodystrophy (PMID: 17660820, 27604306). ClinVar contains an entry for this variant (Variation ID: 449514). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects TREX1 function (PMID: 17660820). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000004403	SCV001934403	pathogenic	Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations	2021-01-28	criteria provided, single submitter	clinical testing
OMIM	RCV000004403	SCV000024575	pathogenic	Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations	2007-09-01	no assertion criteria provided	literature only