Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000211635 | SCV000295373 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Gene |
RCV000497836 | SCV000589575 | likely pathogenic | not provided | 2017-06-08 | criteria provided, single submitter | clinical testing | The S444P variant (reported as S423P due to historic nomenclature) has been reported previously in a few unrelated individuals with familial hypercholesterolemia, two of whom harbored a second LDLR variant (Laurie et al., 2004; Kusters et al., 2013). The S444P variant is not observed in large population cohorts (Lek et al., 2016). The S444P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs within the LDL-receptor class B 2 repeat region. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret S444P as a likely pathogenic variant. |
Cardiovascular Genetics Laboratory, |
RCV000211635 | SCV000268611 | pathogenic | Hypercholesterolemia, familial, 1 | 2008-06-09 | no assertion criteria provided | clinical testing | |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000211635 | SCV000606398 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |