ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.226G>T (p.Gly76Trp) (rs574337291)

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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 RCV000237270 SCV000294538 likely benign Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000237270 SCV000322879 uncertain significance Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research 0/100 normolipidemic individuals
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000237270 SCV000503113 likely pathogenic Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1 , family member = 1 with co-segregation / mild phenotype / Software predictions: Damaging
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000237270 SCV000583641 likely pathogenic Familial hypercholesterolemia 1 2017-03-30 criteria provided, single submitter clinical testing
Color RCV001182218 SCV001347577 likely benign Familial hypercholesterolemia 2017-05-15 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group,Broad Institute RCV001182218 SCV001423041 uncertain significance Familial hypercholesterolemia 2020-01-22 no assertion criteria provided curation The p.Gly76Trp variant in LDLR has been reported in at least 1 Portuguese individual with familial hypercholesterolemia (PMID: 17765246), and was absent from large population studies. This variant has also been reported in ClinVar as having conflicting interpretations of pathogenicity (Variation ID: rs574337291). In vitro functional studies provide some evidence that the p.Gly76Trp variant may not impact protein function (PMID: 25741862). However, these types of assays may not accurately represent biological function. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Gly76Trp variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3, BS3_supporting (Richards 2015).

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