Submissions for variant NM_152443.3(RDH12):c.759del (p.Phe254fs)

dbSNP: rs1594867516

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003769395	SCV004641617	pathogenic	Leber congenital amaurosis 13	2023-12-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Phe254Leufs*24) in the RDH12 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 63 amino acid(s) of the RDH12 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been observed in the literature in individuals with autosomal recessive RDH12-related conditions. This variant has been reported in individual(s) with autosomal dominant retinitis pigmentosa (PMID: 32322264); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 812389). This variant disrupts a region of the RDH12 protein in which other variant(s) (p.Trp304*) have been determined to be pathogenic (PMID: 20736127, 24625443). 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.
Dept Of Ophthalmology, Nagoya University	RCV003890160	SCV004707758	likely pathogenic	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001003157	SCV001161228	pathogenic	Retinitis pigmentosa	2019-06-23	no assertion criteria provided	research
Moosajee Lab, UCL Institute of Ophthalmology	RCV001003157	SCV001164601	pathogenic	Retinitis pigmentosa		no assertion criteria provided	clinical testing	A single base pair deletion [(c.759del; p.(Phe254Leufs*24)] in RDH12 was identified in two unrelated individuals with familial autosomal dominant retinitis pigmentosa. The variant results in a frameshift and premature termination, resulting in loss of the terminal 63 amino acids.