Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001300047 | SCV001489169 | uncertain significance | Leber congenital amaurosis 4 | 2022-06-13 | criteria provided, single submitter | clinical testing | This sequence change affects codon 214 of the AIPL1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the AIPL1 protein. This variant also falls at the last nucleotide of exon 4, which is part of the consensus splice site for this exon. This variant is present in population databases (rs747890893, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with AIPL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1003487). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts the c.642G nucleotide in the AIPL1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 21900377, 26650897). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |