Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV002789986 | SCV003761279 | likely pathogenic | Retinitis pigmentosa 19 | 2023-01-25 | criteria provided, single submitter | curation | The heterozygous p.Phe1880LeufsTer13 variant in ABCA4 was identified by our study, in the compound heterozygous state with a known risk variant (ClinVar Variation ID: 99390), in one individual with retinitis pigmentosa. This individual also carried a known risk variant (ClinVar Variation ID: 99390); however the phase of these variants is unknown at this time. The p.Phe1880LeufsTer13 variant in ABCA4 has been previously reported in one individual with autosomal recessive ABCA4-related retinopathy (PMID: 32893963). This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1880 and leads to a premature termination codon 13 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the ABCA4 gene is an established disease mechanism in autosomal recessive ABCA4-related retinopathy. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive ABCA4-related retinopathy. ACMG/AMP Criteria applied: PVS1, PM2_Supporting (Richards 2015). |
Pars Genome Lab | RCV003229942 | SCV003926616 | pathogenic | Severe early-childhood-onset retinal dystrophy | criteria provided, single submitter | clinical testing |