ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1325A>G (p.Tyr442Cys)

dbSNP: rs879254864
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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 RCV000238215 SCV000295366 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge RCV000238215 SCV000322943 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research 0/208 non-FH alleles; 0/100 healthy control individuals
Robarts Research Institute, Western University RCV000238215 SCV000484727 likely pathogenic Hypercholesterolemia, familial, 1 criteria provided, single submitter clinical testing
Ambry Genetics RCV003298315 SCV004000127 likely pathogenic Cardiovascular phenotype 2023-05-25 criteria provided, single submitter clinical testing The p.Y442C variant (also known as c.1325A>G), located in coding exon 9 of the LDLR gene, results from an A to G substitution at nucleotide position 1325. The tyrosine at codon 442 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration, which is also known as p.Y421C, has been reported in individuals with familial hypercholesterolemia (FH) (Wang J et al. J Lipid Res, 2005 Feb;46:366-72; Medeiros AM et al. Atherosclerosis, 2010 Oct;212:553-8; Tada H et al. J Clin Lipidol, 2020 Mar;14:346-351.e9; Ambry internal data). Another alteration at the same codon, p.Y442H (c.1324T>C), has been detected in individuals with definite or suspected FH (Widhalm K et al. J Inherit Metab Dis, 2007 Apr;30:239-47; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000238215 SCV000606394 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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