ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1215C>G (p.Asn405Lys) (rs879254837)

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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 RCV000238220 SCV000295304 likely pathogenic Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000238220 SCV000503316 likely pathogenic Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1 / previously described in association with FH / Software predictions: Conflicting
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000238220 SCV000583805 pathogenic Familial hypercholesterolemia 1 2017-03-30 criteria provided, single submitter clinical testing
Invitae RCV000791392 SCV000824745 likely pathogenic Familial hypercholesterolemia 2018-12-03 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 405 of the LDLR protein (p.Asn405Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with hypercholesterolemia, segregating with the disease in a single family (PMID: 9237502, 29576406, Invitae). This variant is also known in the literature as p.Asn384Lys. ClinVar contains an entry for this variant (Variation ID: 251738). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000238220 SCV000606360 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research

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