Submissions for variant NM_006269.2(RP1):c.2305A>T (p.Lys769Ter)

dbSNP: rs1488237523

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV001074169	SCV001239739	likely pathogenic	Retinal dystrophy	2019-02-19	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001862542	SCV002156302	pathogenic	not provided	2022-03-09	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys769*) in the RP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1388 amino acid(s) of the RP1 protein. This variant has not been reported in the literature in individuals affected with RP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 866299). This variant disrupts a region of the RP1 protein in which other variant(s) (p.Ile2061Serfs*12) have been determined to be pathogenic (PMID: 11527933, 19933189, 29425069, 30027431). 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.
CeGaT Center for Human Genetics Tuebingen	RCV001862542	SCV002545618	likely pathogenic	not provided	2022-04-01	criteria provided, single submitter	clinical testing	RP1: PVS1:Strong, PM2, PP4