SLC24A1

Inheritance Pattern: AR

Disease ID:MONDO:0013450

Submitter: PanelApp Australia

Inheritance Pattern: AR

Disease ID:MONDO:0019118

Submitter: ClinGen

*SLC24A1* was first reported in relation to autosomal recessive congenital stationary night blindness (CSNB) in 2010 (Riazuddin et al., PMID: 20850105). Patients with CSNB mainly experience night blindness, however depending upon the clinical classification of CSNB, other ocular features including reduced visual acuity, photophobia, myopia, nystagmus, and strabismus have also been reported (PMID: 26822852). Disease-causing variants in *SLC24A1* have been implicated in autosomal recessive retinitis pigmentosa as well (PMIDs: 27624628, 35486108, 36729443). Despite variability in phenotypic features, the cases share overlapping phenotypes consistent with a single spectrum of disease. No differences in inheritance patterns or disease mechanisms were observed. Therefore, per criteria outlined by the ClinGen Lumping & Splitting Working Group, cases of congenital stationary night blindness (complete) 1D (MIM#: 613830) or retinitis pigmentosa caused by biallelic *SLC24A1* variants have been lumped together into a single disease entity referred to as SLC24A1-related retinopathy. Seven variants (including, missense, in-frame indel, nonsense, and frameshift) that have been reported in seven probands in four publications (PMIDs: 20850105, 26822852, 35486108, and 35446361) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is known to be loss of function. This gene-disease relationship is also supported by experimental evidence including a mouse model (PMID: 26246500) and expression studies (PMID: 20850105). In mice, the expression of *Slc24a1* was detected in the retina around postnatal day 7. *In-situ* hybridization and immunohistological studies localized *Slc24a1* to the inner segment, outer and inner nuclear layers, and ganglion cells of the mouse retina (PMID: 20850105). A mouse model in which *Slc24a1* was deleted showed abnormally formed outer segment disks, suppressed expression, and function of rod CNG channels, which resulted in a 100-fold reduction in rod responses, whereas cone responses were normal (PMID: 26246500, 35446361). In summary, there is definitive evidence supporting the relationship between *SLC24A1* and autosomal recessive SLC24A1-related retinopathy. This has been repeatedly demonstrated in research and clinical diagnostic settings and upheld over time without the emergence of contradictory evidence. This classification was approved by the ClinGen Retina GCEP on the meeting date September 5th, 2024 (SOP Version 10).

Inheritance Pattern: AR

Disease ID:MONDO:0013450

Submitter: Labcorp Genetics (formerly Invitae)