Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004766597 | SCV005381371 | pathogenic | Polycystic kidney disease, adult type | 2024-08-06 | criteria provided, single submitter | clinical testing | Variant summary: The variant involves the deletion of exons 27-46 in the PKD1 gene. A presumed nomenclature of c.(9397+1_9398-1)_(*1020_?)del has been designated for the purposes of this classification. The exact breakpoint at the distal 3' end of this variant is unknown, therefore this deletion may extend downstream of the annotated region of the gene. As it encompasses the termination codon, it is predicted to escape nonsense mediated decay (NMD). The variant was absent in 21684 control chromosomes (gnomAD Structural Variants database). Deletion of exon 27-46 has been reported in the literature (as a part of a larger deletion that also included TSC2), in an individual affected with TSC2/PKD1 contiguous gene deletion syndrome (example: Matsubara_2021). Additionally, another variant (c.11249G>A; p.Arg3750Gln) within the deleted region has been classified as pathogenic by our laboratory, indicating the functional significance of the deleted protein region. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 33581549). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic. |