ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.270T>A (p.Asp90Glu) (rs372828849)

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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 RCV000238563 SCV000294572 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 RCV000238563 SCV000503124 pathogenic Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1 , family members = 8 with co-segregation / other mutations at same codon / Software predictions: Damaging
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000238563 SCV000583647 pathogenic Familial hypercholesterolemia 1 2017-03-30 criteria provided, single submitter clinical testing
Invitae RCV001057934 SCV001222461 likely pathogenic Familial hypercholesterolemia 2019-12-26 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 90 of the LDLR protein (p.Asp90Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with familial hypercholesterolemia (PMID: 20809525, 27824480, Invitae). ClinVar contains an entry for this variant (Variation ID: 251107). 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 C0"). This variant disrupts the p.Asp90 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25962062, 21376320, 27765764, 15823276, 16343504, 12837857, 12436241, 11857755, 9026534). 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 RCV000238563 SCV000606059 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research

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