ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1468T>C (p.Trp490Arg) (rs730880130)

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Total submissions: 6
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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 1 2016-03-25 criteria provided, single submitter literature only
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000157290 SCV000322956 pathogenic Familial hypercholesterolemia 1 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 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
Invitae RCV001034638 SCV000752409 likely pathogenic Familial hypercholesterolemia 2019-02-06 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, Invitae). This variant is also described as Trp469Arg (W469R) in the literature. ClinVar contains an entry for this variant (Variation ID: 180402). This variant has been reported to affect LDLR protein function (PMID: 23021490, 25386756). 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.
Brunham Lab, Centre for Heart and Lung Innovation,University of British Columbia RCV000157290 SCV001432634 likely pathogenic Familial hypercholesterolemia 1 2019-03-13 criteria provided, single submitter research
Blueprint Genetics RCV000157290 SCV000207021 pathogenic Familial hypercholesterolemia 1 2014-11-27 no assertion criteria provided clinical testing

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