ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1329G>T (p.Trp443Cys)

dbSNP: rs879254867
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000238274 SCV000295372 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Robarts Research Institute, Western University RCV000238274 SCV000484760 likely pathogenic Hypercholesterolemia, familial, 1 criteria provided, single submitter clinical testing
Invitae RCV001857827 SCV002174157 pathogenic Familial hypercholesterolemia 2023-10-18 criteria provided, single submitter clinical testing This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 443 of the LDLR protein (p.Trp443Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hypercholesterolemia (PMID: 9727746, 11196104, 22390909). This variant is also known as p.Trp422Cys. ClinVar contains an entry for this variant (Variation ID: 251793). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LDLR protein function. For these reasons, this variant has been classified as Pathogenic.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000238274 SCV000606397 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000238274 SCV000733820 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV001699172 SCV001922787 pathogenic not provided no assertion criteria provided clinical testing

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