Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003041354 | SCV003443167 | pathogenic | Familial hypercholesterolemia | 2023-07-14 | criteria provided, single submitter | clinical testing | This variant, c.1885_1889delinsGATCATCAACC, is a complex sequence change that results in the deletion of 2 and insertion of 4 amino acid(s) in the LDLR protein (p.Phe629_Ser630delinsAspHisGlnPro). This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with familial hypercholesterolemia (PMID: 29228028; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2138230). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects LDLR function (PMID: 29228028). This variant disrupts a region of the LDLR protein in which other variant(s) (p.Phe629Cys) have been determined to be pathogenic (PMID: 23375686; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |