ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.932A>G (p.Lys311Arg) (rs761765254)

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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 RCV000238436 SCV000503256 likely pathogenic Familial hypercholesterolemia 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 3 , family members = 2 with co-segregation c.932A>G, c.939C>G / p.Lys311Arg, p.Cys313Trp systematicaly associated (Van Leuven et al. Atherosclerosis 2001) / Software predictions: Conflicting
Invitae RCV000791455 SCV000830603 uncertain significance Familial hypercholesterolemias 2018-08-13 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 311 of the LDLR protein (p.Lys311Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with hypercholesterolemia (PMID: 1301940, 15523646, 20506408 ). This variant is also known as K290R in the literature. ClinVar contains entries for this variant (Variation ID: 251532, 430769). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000238436 SCV000295064 likely benign Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000238436 SCV000606272 pathogenic Familial hypercholesterolemia no assertion criteria provided research

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