Submissions for variant NM_005802.5(TOPORS):c.2539C>T (p.Arg847Ter)

dbSNP: rs869312183

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV001090491	SCV001246069	pathogenic	not provided	2016-10-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001090491	SCV001826046	likely pathogenic	not provided	2019-07-26	criteria provided, single submitter	clinical testing	Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 199 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 33576794, 28453362, 26155838, 22581970, 26872967)
Invitae	RCV001090491	SCV003440881	pathogenic	not provided	2022-10-23	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 224754). For these reasons, this variant has been classified as Pathogenic. This protein change is located in a region of the TOPORS protein where a significant number of previously reported TOPORS nonsense and frameshift mutations are found (PMID: 18509552, 23950152, 28076437, 17924349). These observations suggest that a previously unreported nonsense or frameshift change within this region may affect protein function, but experiments have not been done to test this possibility. This variant is also known as p.R782X. This premature translational stop signal has been observed in individuals with retinitis pigmentosa (PMID: 22581970, 26155838, 28453362). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg847*) in the TOPORS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 199 amino acid(s) of the TOPORS protein.
Dept Of Ophthalmology, Nagoya University	RCV000210308	SCV004706792	likely pathogenic	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals	RCV000210308	SCV000259097	likely pathogenic	Retinal dystrophy	2015-01-30	no assertion criteria provided	clinical testing