ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1394A>G (p.Tyr465Cys)

dbSNP: rs879254889
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000238401 SCV000295411 uncertain significance Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation RCV000238401 SCV000540816 likely pathogenic Hypercholesterolemia, familial, 1 2016-11-05 criteria provided, single submitter clinical testing
Invitae RCV001213617 SCV001385254 uncertain significance Familial hypercholesterolemia 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 465 of the LDLR protein (p.Tyr465Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with familial hypercholesterolemia (PMID: 22698793, 33740630). ClinVar contains an entry for this variant (Variation ID: 251826). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000238401 SCV000606414 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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