ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2430G>A (p.Trp810Ter)

dbSNP: rs879255210
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000238147 SCV000296006 pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
GeneDx RCV000483979 SCV000568514 pathogenic not provided 2017-12-19 criteria provided, single submitter clinical testing The W810X variant in the LDLR gene has been reported as a novel variant in one patient with FH (Fouchier et al., 2005). This variant is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the LDLR gene have been reported in Human Gene Mutation Database in association with FH (Stenson et al., 2014). Furthermore, the W810X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server)
CeGaT Center for Human Genetics Tuebingen RCV000483979 SCV001246013 pathogenic not provided 2019-01-01 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000238147 SCV001429207 pathogenic Hypercholesterolemia, familial, 1 2019-08-13 criteria provided, single submitter clinical testing
Brunham Lab, Centre for Heart and Lung Innovation, University of British Columbia RCV000238147 SCV001432639 pathogenic Hypercholesterolemia, familial, 1 2019-05-11 criteria provided, single submitter research
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000483979 SCV001762193 pathogenic not provided 2021-06-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001854912 SCV002240861 pathogenic Familial hypercholesterolemia 2023-12-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp810*) 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: 16250003). ClinVar contains an entry for this variant (Variation ID: 252335). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV004639198 SCV005135993 pathogenic Cardiovascular phenotype 2024-05-24 criteria provided, single submitter clinical testing The p.W810* pathogenic mutation (also known as c.2430G>A), located in coding exon 17 of the LDLR gene, results from a G to A substitution at nucleotide position 2430. This changes the amino acid from a tryptophan to a stop codon within coding exon 17. This pathogenic variant has been reported in association with familial hypercholesterolemia (FH) (Fouchier SW et al. Hum Mutat, 2005 Dec;26:550-6; Meshkov A et al. Genes (Basel), 2021 Jan;12:). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000238147 SCV000606651 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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