ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1998G>A (p.Trp666Ter)

dbSNP: rs752935814
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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 RCV000237406 SCV000295807 pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation RCV000237406 SCV000540850 pathogenic Hypercholesterolemia, familial, 1 2016-11-05 criteria provided, single submitter clinical testing
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000237406 SCV000583917 pathogenic Hypercholesterolemia, familial, 1 2017-03-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV002418060 SCV002720063 pathogenic Cardiovascular phenotype 2017-10-20 criteria provided, single submitter clinical testing The p.W666* pathogenic mutation (also known as c.1998G>A), located in coding exon 14 of the LDLR gene, results from a G to A substitution at nucleotide position 1998. This changes the amino acid from a tryptophan to a stop codon within coding exon 14. This alteration, also referred to as p.W645*, has been reported in individuals with hypercholesterolemia (Kuhrová V et al. Hum. Mutat., 2002 Jan;19:80; Humphries SE et al. J. Mol. Med., 2006 Mar;84:203-14; Marduel M et al. Hum. Mutat., 2010 Nov;31:E1811-24). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae RCV002518492 SCV003443168 pathogenic Familial hypercholesterolemia 2023-10-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp666*) in the LDLR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with familial hypercholesterolemia (PMID: 11754108, 33418990). This variant is also known as W645X. ClinVar contains an entry for this variant (Variation ID: 252161). For these reasons, this variant has been classified as Pathogenic.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237406 SCV000606572 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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