ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.283T>C (p.Cys95Arg)

dbSNP: rs879254456
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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 RCV000237550 SCV000294576 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Arcensus RCV000237550 SCV002564608 pathogenic Hypercholesterolemia, familial, 1 2013-02-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV002436070 SCV002751749 pathogenic Cardiovascular phenotype 2023-03-20 criteria provided, single submitter clinical testing The c.283T>C (p.C95R) alteration is located in exon 3 (coding exon 3) of the LDLR gene. This alteration results from a T to C substitution at nucleotide position 283, causing the cysteine (C) at amino acid position 95 to be replaced by an arginine (R). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Pathogenic LDLR mutations that result in the substitution or generation of cysteine residues within the cysteine-rich LDLR class A repeats and EGF-like domains are common in familial hypercholesterolemia (FH) (Villéger, 2002). This particular cysteine alteration (also referred to as p.C74R) has been detected in several individuals with FH (Deiana, 2000; Fouchier, 2005; Blesa, 2006; Vandrovcova, 2013). A different variant affecting this codon (p.C95F, c.284G>T) has also been reported in association with FH (Miyake, 2009). Internal structural analysis indicates this alteration eliminates a disulfide bond critical for the structural integrity of LDLR class A repeat 2 (Ambry internal data). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237550 SCV000606061 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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