Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001184966 | SCV001351069 | likely benign | Familial hypercholesterolemia | 2019-10-24 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001184966 | SCV001615071 | likely pathogenic | Familial hypercholesterolemia | 2024-10-15 | criteria provided, single submitter | clinical testing | This sequence change affects codon 181 of the LDLR mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LDLR protein. This variant is present in population databases (rs766577671, gnomAD 0.002%). This variant has been observed in individual(s) with clinical features of LDLR-related conditions (internal data). Invitae Evidence Modeling of clinical and family history, age, sex, and reported ancestry of multiple individuals with this LDLR variant has been performed. This variant is expected to be pathogenic with a positive predictive value of at least 99%. This is a validated machine learning model that incorporates the clinical features of 363,995 individuals referred to our laboratory for LDLR testing. ClinVar contains an entry for this variant (Variation ID: 440579). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Ambry Genetics | RCV002350130 | SCV002652260 | likely benign | Cardiovascular phenotype | 2022-08-22 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| All of Us Research Program, |
RCV000508791 | SCV004820177 | likely benign | Hypercholesterolemia, familial, 1 | 2023-10-23 | criteria provided, single submitter | clinical testing | |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000508791 | SCV000606155 | benign | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |