ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1845G>A (p.Glu615=) (rs879255047)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000237596 SCV000503422 likely pathogenic Familial hypercholesterolemia 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1
Iberoamerican FH Network RCV000237596 SCV000748155 uncertain significance Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research
Invitae RCV000237596 SCV000752417 uncertain significance Familial hypercholesterolemia 2017-10-21 criteria provided, single submitter clinical testing This sequence change affects codon 615 of the LDLR mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LDLR protein. This variant also falls at the last nucleotide of exon 12 of the LDLR coding sequence, which is part of the consensus splice site for this exon. Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with familial hypercholesterolaemia  (PMID: 17539906). This variant is also known as IVS13-2G>A in the literature.  ClinVar contains an entry for this variant (Variation ID: 252065). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
LDLR-LOVD, British Heart Foundation RCV000237596 SCV000295696 likely pathogenic Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only

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