ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1297G>C (p.Asp433His)

dbSNP: rs121908036
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000003930 SCV000295350 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Fundacion Hipercolesterolemia Familiar RCV000003930 SCV000607582 pathogenic Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001851630 SCV002176476 pathogenic Familial hypercholesterolemia 2022-08-09 criteria provided, single submitter clinical testing Experimental studies have shown that this missense change affects LDLR function (PMID: 1446662). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 433 of the LDLR protein (p.Asp433His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with familial hypercholesterolemia (PMID: 1446662, 31491741). It has also been observed to segregate with disease in related individuals. This variant is also known as p.Asp412His. ClinVar contains an entry for this variant (Variation ID: 3732). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000003930 SCV000024095 pathogenic Hypercholesterolemia, familial, 1 1992-11-15 no assertion criteria provided literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000003930 SCV000606385 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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