Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000237407 | SCV000295268 | likely benign | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Invitae | RCV000864649 | SCV001005478 | likely benign | Familial hypercholesterolemia | 2023-08-14 | criteria provided, single submitter | clinical testing | |
Gene |
RCV002225535 | SCV002504161 | likely benign | not provided | 2019-12-12 | criteria provided, single submitter | clinical testing | See Variant Classification Assertion Criteria. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003226266 | SCV003922714 | uncertain significance | not specified | 2023-03-21 | criteria provided, single submitter | clinical testing | Variant summary: LDLR c.1186+11G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. One in-silico tool predicts a benign effect on splicing for this variant (Trap Score: 0.019). The variant allele was found at a frequency of 4e-06 in 248464 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1186+11G>A has been reported in the literature in an individual who had plasma cholesterol in the 20th percentile (example: Alharbi_ 2005). This report does not provide unequivocal conclusions about association of the variant with Familial Hypercholesterolemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |