ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.-152C>T

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237330 SCV000294380 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000237330 SCV000588474 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research
Invitae RCV001258114 SCV000752416 pathogenic Familial hypercholesterolemia 2023-12-30 criteria provided, single submitter clinical testing This variant occurs in a non-coding region of the LDLR gene. It does not change the encoded amino acid sequence of the LDLR protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with familial hypercholesterolemia (PMID: 10484771, 11005141, 16542394; Invitae). This variant is also known as c.-59C>T. ClinVar contains an entry for this variant (Variation ID: 250945). Studies have shown that this variant alters LDLR gene expression (PMID: 10484771). For these reasons, this variant has been classified as Pathogenic.
Brunham Lab, Centre for Heart and Lung Innovation, University of British Columbia RCV000237330 SCV001432656 uncertain significance Hypercholesterolemia, familial, 1 2019-03-03 criteria provided, single submitter research
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV001258114 SCV001434981 likely pathogenic Familial hypercholesterolemia 2019-04-30 criteria provided, single submitter clinical testing The c.-152C>T variant in the LDLR gene sits upstream of the coding region and is predicted to reduce promoter activity of the gene. This variant is not observed in general population databases but has been reported in multiple unrelated individuals with familial hypercholesterolemia (PMID: 11005141, 16542394). Functional studies have shown reduced promoter activity of the LDLR gene when this variant is present (PMID: 10484771). The c.-152C>T variant in the LDLR gene is classified as likely pathogenic.
Ambry Genetics RCV002401929 SCV002706639 likely pathogenic Cardiovascular phenotype 2021-03-26 criteria provided, single submitter clinical testing The c.-152C>T variant is located in the 5' untranslated region (5’ UTR) of the LDLR gene. This variant results from a C to T substitution 152 bases upstream from the first translated codon. This variant (also described as c.-59C>T) has been reported in individuals with familial hypercholesterolemia (Scholtz CL et al. Hum Mol Genet, 1999 Oct;8:2025-30; Khoo KL et al. Clin Genet, 2000 Aug;58:98-105; Brusgaard K et al. Clin Genet, 2006 Mar;69:277-83). Functional studies showed reduction in promoter activity and transcription (Scholtz CL et al. Hum Mol Genet, 1999 Oct;8:2025-30; Kircher M et al. Nat Commun, 2019 08;10:3583). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
All of Us Research Program, National Institutes of Health RCV000237330 SCV004836275 likely pathogenic Hypercholesterolemia, familial, 1 2023-12-15 criteria provided, single submitter clinical testing This variant has been reported in multiple individuals with familial hypercholesterolemia (PMID: 10484771, 16250003, 16542394, 30293936, 34037665). It has been reported to co-segregate with disease in one family (PMID: 10484771). This variant is absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Functional studies suggest that this variant has a deleterious effect on the protein (PMID: 10484771).
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237330 SCV000605984 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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