ClinVar

Description

Variant summary: The variant involves the deletion of exon 2 in the RP1L1 gene. A presumed nomenclature of c.(-20+1_-19-1)_(609+1_610-1)del has been designated for the purposes of this classification. The exact breakpoint at the 5' end of this variant is unknown, therefore this deletion may extend upstream of the annotated region of this gene. Although the exact breakpoints of this deletion are not known, it is predicted to remove the initiation codon and result in an absence of protein or a truncation of the encoded protein due to translation initiation at a downstream site. Current evidence is not sufficient to establish loss of function as a mechanism for disease. The variant allele was found at a frequency of 5.9e-05 in 119612 control chromosomes in the gnomAD database (Structural Variants v4.1 dataset). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.(-20+1_-19-1)_(609+1_610-1)del in individuals affected with RP1L1-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 3245617). Based on the evidence outlined above, the variant was classified as uncertain significance.