ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1463T>A (p.Ile488Asn) (rs879254913)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237707 SCV000295447 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 RCV000237707 SCV000503351 likely pathogenic Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 2 , family members = 3 /FH-Fiacenza/Software predictions: Conflicting
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000237707 SCV000583834 pathogenic Familial hypercholesterolemia 1 2017-03-30 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781505 SCV000919587 pathogenic Familial hypercholesterolemia 2018-10-22 criteria provided, single submitter clinical testing Variant summary: LDLR c.1463T>A (p.Ile488Asn) results in a non-conservative amino acid change located in the LDLR class B repeat of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 246228 control chromosomes (gnomAD and publications). The variant, c.1463T>A, has been reported in the literature in individuals affected with Familial Hypercholesterolemia (Bertolini_2013, Garcia-Garcia_2001, Wintjens_2016). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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