ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1688C>A (p.Pro563His)

dbSNP: rs879254987
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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 RCV000237354 SCV000295578 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001800608 SCV002047013 uncertain significance not provided 2021-04-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV002401940 SCV002712678 uncertain significance Cardiovascular phenotype 2021-01-07 criteria provided, single submitter clinical testing The p.P563H variant (also known as c.1688C>A and legacy p.P542H), located in coding exon 11 of the LDLR gene, results from a C to A substitution at nucleotide position 1688. The proline at codon 563 is replaced by histidine, an amino acid with similar properties. This variant has been reported in overlapping Dutch familial hypercholesterolemia cohorts, including one study where it was detected in a pediatric case with autosomal dominant hypercholesterolemia; however, specific clinical details were limited (Lombardi MP et al. Clin Genet, 2000 Feb;57:116-24; Fouchier SW et al. Hum Genet, 2001 Dec;109:602-15; van der Graaf A et al. Circulation, 2011 Mar;123:1167-73). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237354 SCV000606483 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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