ClinVar

Description

Variant summary: The variant identified by MLPA or other technology involves the duplication of exons 79-83 in the ADGRV1 gene. A presumed nomenclature of c.(17019+1_17020-1)_(17856+1_17857-1)dup has been designated for the purposes of this classification. It has been assumed that this is a tandem duplication in direct orientation (Richardson_GIM_2018, Newman_AJHG_2015). Although exact breakpoints of this duplication are not known, it is expected to result in a large in-frame duplication change in the ADGRV1 gene. The variant was absent in 21694 control chromosomes (gnomAD database, Structural Variants dataset). The variant has been reported in the literature in at least 3 individuals affected with Usher Syndrome, described in homozygous state, or together with a second (likely) pathogenic variant (Besnard_2012, Aparisi_2014, Fuster-Garcia_2018), although parental testing was not reported to be performed to determine the phase of these variants. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.