SLC7A14

Inheritance Pattern: AD

Disease ID:MONDO:0019200

Submitter: Orphanet

Inheritance Pattern: AR

Disease ID:MONDO:0014323

Submitter: ClinGen

*SLC7A14* was first reported in relation to autosomal recessive “retinitis pigmentosa 68” in 2014 (Jin et al, 2014, PMID: 24670872). Seven individuals have been reported with bi-allelic variants in this gene. All of these individuals are Chinese with onset of symptoms in childhood, and all are either homozygous for c.988G>A (p.Gly330Arg) or c.1391G>T (p.Cys464Phe), or compound heterozygous for one of those variants and another missense variant (Jin et al, 2014, PMID: 24670872; Guo et al, 2019, PMID: 30924391). Evidence suggests that the p.Gly330Arg variant affects protein localization (Jin et al, 2014, PMID: 24670872; Giffen et al, 2022, PMID: 35394837). In gnomAD v4.1.0, c.988G>A (p.Gly330Arg) and c.1391G>T (p.Cys464Phe) have minor allele frequencies (MAFs) in the East Asian population of 0.02079 (933/44,880 alleles, 11 homozygotes) and 0.01146 (514/44,856 alleles, 3 homozygotes), respectively. The ClinGen Retina Gene Curation Expert Panel considers these MAFs to be too high for these variants to be disease-causing. Additional studies have been conducted in Chinese and Japanese cohorts with retinopathy and no individuals with rare biallelic variants in SLC7A14 were identified (Sugahara et al, 2017, PMID: 27028480; Dan et al, 2020, PMID: 31960602). Individuals with heterozygous missense variants in these genes have been reported, but the clinical significance is unknown. Regarding experimental evidence, in mice, *SLC7A14* is mainly expressed in the brain, spinal cord and retina (inner nuclear layer and photoreceptor layer) (Jin et al, 2014, PMID: 24670872). The gene has a similar expression pattern in zebrafish. Knock-out mice, and knock in mice with the p.Gly330Arg variant exhibit abnormal ERGs and thinning of the retina, in addition to progressive hearing loss, recapitulating the disease phenotype in humans (Jin et al, 2014, PMID: 24670872; Giffen et al, 2022, PMID: 35394837). Zebrafish in which Slc7a14 expression has been knocked down using a morpholino approach tended to have small eyes and had an abnormal response to light-dark transitions (Jin et al, 2014, PMID: 24670872, Zhuang et al, 2019, PMID: 31921845). In summary, based on the high minor allele frequencies for the c.988G>A (p.Gly330Arg) and c.1391G>T (p.Cys464Phe) variants, the evidence supporting the relationship between *SLC7A14* and autosomal recessive “retinitis pigmentosa 68” has been disputed by the ClinGen Retina GCEP. More evidence is needed to either support or entirely refute the role that *SLC7A14* plays in this disease. This classification was approved by the ClinGen Retina GCEP on July 8, 2026 (SOP v12).

Inheritance Pattern: AR

Disease ID:MONDO:0014323

Submitter: PanelApp Australia

Inheritance Pattern: Unknown

Disease ID:MONDO:0014323

Submitter: Labcorp Genetics (formerly Invitae)

Inheritance Pattern: AR

Disease ID:MONDO:0014323

Submitter: G2P