Submissions for variant NM_006269.2(RP1):c.1986del (p.Lys663fs)

gnomAD frequency: 0.00002  dbSNP: rs754246929

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001885189	SCV002138553	pathogenic	not provided	2021-04-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys663Argfs*19) in the RP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1494 amino acid(s) of the RP1 protein. This variant is present in population databases (rs754246929, ExAC 0.009%). This variant has been observed in individual(s) with clinical features of retinitis pigmentosa (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant disrupts the C-terminus of the RP1 protein. Many variants that disrupt this region have been reported in individuals with either autosomal dominant or autosomal recessive retinitis pigmentosa (PMID: 11527933, 19933189, 29425069, 30027431). Therefore, variants that disrupt this region are expected to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel	RCV003324568	SCV004030298	pathogenic	Retinitis pigmentosa	2023-07-24	criteria provided, single submitter	research	Clinical significance based on ACMG v2.0