Submissions for variant NM_006269.2(RP1):c.2219C>G (p.Ser740Ter)

dbSNP: rs1554519555

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000760556	SCV000890447	likely pathogenic	not provided	2018-11-05	criteria provided, single submitter	clinical testing	The S740X variant in the RP1 gene has been reported previously in an individual with retinitis pigmentosa who did not have a second RP1 variant identified (Carss et al., 2017). This variant is predicted to cause loss of normal protein function through protein truncation, as the last 1,417 amino acids are lost. The S740X variant is not observed in large population cohorts (Lek et al., 2016). We interpret S740X as a likely pathogenic variant.
Invitae	RCV000760556	SCV003440745	pathogenic	not provided	2022-08-21	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 437952). This premature translational stop signal has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 28041643, 32783370, 33576794). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser740*) in the RP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1417 amino acid(s) of the RP1 protein.
Dept Of Ophthalmology, Nagoya University	RCV003889913	SCV004706702	likely pathogenic	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000505089	SCV000598685	likely pathogenic	Retinitis pigmentosa	2015-01-01	no assertion criteria provided	research