ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1690A>G (p.Asn564Asp) (rs397509365)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000238267 SCV000295580 likely pathogenic Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Robarts Research Institute,Western University RCV000238267 SCV000484717 likely pathogenic Familial hypercholesterolemia 1 criteria provided, single submitter clinical testing
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000238267 SCV000503385 likely pathogenic Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 3 , family member = 1 / /Software predictions: Conflicting
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000238267 SCV000583863 pathogenic Familial hypercholesterolemia 1 2017-03-30 criteria provided, single submitter clinical testing
Color Health, Inc RCV001177566 SCV001341796 uncertain significance Familial hypercholesterolemia 2019-07-30 criteria provided, single submitter clinical testing
Invitae RCV001177566 SCV001374151 likely pathogenic Familial hypercholesterolemia 2020-07-31 criteria provided, single submitter clinical testing This sequence change replaces asparagine with aspartic acid at codon 564 of the LDLR protein (p.Asn564Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with familial hypercholesterolemia (PMID: 16250003, Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 251973). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C1). This variant disrupts the p.Asn564 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9654205, 18718593, 20538126, 23375686, 28145427). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 RCV000238267 SCV000606485 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research

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