ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1003G>A (p.Gly335Ser) (rs544453230)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000238015 SCV000599356 likely pathogenic Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter curation
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000238015 SCV000503276 likely benign Familial hypercholesterolemia 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1 / Software predictions: Damaging
Dept. of Genetics and Pharmacogenomics, Merck Research Labs RCV000161976 SCV000189551 not provided not provided no assertion provided in vitro
Division of Human Genetics,Children's Hospital of Philadelphia RCV000238015 SCV000536701 likely pathogenic Familial hypercholesterolemia 2014-10-31 no assertion criteria provided research
Iberoamerican FH Network RCV000238015 SCV000748093 likely pathogenic Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research
Invitae RCV000238015 SCV000819690 likely pathogenic Familial hypercholesterolemia 2018-05-13 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 335 of the LDLR protein (p.Gly335Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs544453230, ExAC 0.01%). This variant has been observed in several individuals affected with familial hypercholesterolemia (FH) (PMID: 1301956, 23375686, 11668627, 28502510, 28008010, 27765764, 15556094) and individuals with myocardial infarction (PMID: 25647241, 25487149). This variant was shown to segregate with FH in a family that also carried another pathogenic variant in LDLR (PMID: 27578127). It is also known as G314S in the literature. ClinVar contains an entry for this variant (Variation ID: 183105). Experimental studies have shown that this missense change on LDLR activity is inconsistent (PMID: 1301956, 25647241). The observation of one or more missense substitutions at this codon (p.Gly335Val) in affected individuals suggests that this may be a clinically significant residue (PMID: 10735632). 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.
LDLR-LOVD, British Heart Foundation RCV000238015 SCV000295129 likely pathogenic Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000215066 SCV000271915 uncertain significance not specified 2019-01-15 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Robarts Research Institute,Western University RCV000238015 SCV000484723 likely pathogenic Familial hypercholesterolemia criteria provided, single submitter clinical testing
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000238015 SCV000583773 pathogenic Familial hypercholesterolemia 2017-03-30 criteria provided, single submitter clinical testing

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