Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004526446 | SCV005040082 | pathogenic | Stargardt disease | 2024-03-07 | criteria provided, single submitter | clinical testing | Variant summary: ABCA4 c.5351T>C (p.Leu1784Pro) results in a non-conservative amino acid change located in the ABC-2 type transporter, transmembrane domain (IPR013525) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251452 control chromosomes. c.5351T>C has been reported in the literature in at least 4 compound heterozygous individuals affected with Stargardt Disease (e.g., Nacissi_2018, Whelan_2020). These data indicate that the variant is likely to be associated with disease. Additionally, other variants at the Leu1784 residue have been reported as associated with disease (p.Leu1784Arg), suggesting that this codon is functionally important. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 30060493, 31963381). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Fulgent Genetics, |
RCV005023562 | SCV005663276 | pathogenic | Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19 | 2024-03-08 | criteria provided, single submitter | clinical testing |