ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1124A>G (p.Tyr375Cys) (rs879254800)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237921 SCV000295235 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 RCV000237921 SCV000503302 likely pathogenic Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 3 , family members = 4 with co-segregation / previously described in association with FH / Software predictions: Damaging
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000237921 SCV000583792 pathogenic Familial hypercholesterolemia 1 2017-03-30 criteria provided, single submitter clinical testing
Fundacion Hipercolesterolemia Familiar RCV000237921 SCV000607561 likely pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Fulgent Genetics,Fulgent Genetics RCV000237921 SCV000894173 pathogenic Familial hypercholesterolemia 1 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001063149 SCV001227983 pathogenic Familial hypercholesterolemia 2019-03-15 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 375 of the LDLR protein (p.Tyr375Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with familial hypercholesterolemia in a family (PMID: 9195230) and in individuals affected with this condition (PMID: 11668640, 15823288). This variant is also known as Y354C in the literature. ClinVar contains an entry for this variant (Variation ID: 251679). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000237921 SCV001433510 likely pathogenic Familial hypercholesterolemia 1 2019-09-05 criteria provided, single submitter clinical testing

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