Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001031075 | SCV001194381 | pathogenic | Familial hypercholesterolemia | 2019-09-09 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 16-18 of the LDLR gene. The 5' boundary is likely confined to intron 15. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. A similar deletion of exons 16-18 has been observed to segregate with hypercholesterolemia in families (PMID: 1362925), and has been reported in several other affected individuals, particularly in Finnish populations (PMID: 1372927, 16250003, 18718593, 20828696, 29693183). This variant is also known as FH-Helsinki in the literature. A similar deletion of exons 16-18 has been reported to affect LDLR protein function in patient-derived fibroblasts (PMID: 2760198). For these reasons, this variant has been classified as Pathogenic. |