ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1468T>C (p.Trp490Arg) (rs730880130)

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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 RCV000157290 SCV000295452 likely pathogenic Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000157290 SCV000322956 pathogenic Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research 0/208 non-FH alleles
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000157290 SCV000503352 likely pathogenic Familial hypercholesterolemia 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
Invitae RCV000157290 SCV000752409 uncertain significance Familial hypercholesterolemia 2017-11-15 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with arginine at codon 490 of the LDLR protein (p.Trp490Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with familial hypercholesterolemia (PMID: 17765246, 23375686, 23021490). ClinVar contains an entry for this variant (Variation ID: 180402). Experimental studies have shown that this missense change results in abrogated LDLR activity and a significant reduction of cell surface receptor expression due to a severe defect in trafficking of the LDLR protein (PMID: 25386756). 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.
Blueprint Genetics RCV000157290 SCV000207021 pathogenic Familial hypercholesterolemia 2014-11-27 no assertion criteria provided clinical testing

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