ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.296C>G (p.Ser99Ter) (rs377271627)

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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 RCV000238369 SCV000294586 pathogenic Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only
Invitae RCV000775030 SCV000544657 pathogenic Familial hypercholesterolemias 2018-12-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 99 (p.Ser99*) of 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. This particular variant has been reported in the literature in many individuals with familial hypercholesterolemia (PMID: 7718019, 9259195, 9698020, 11857755, 23375686). This variant is also known as p.Ser78* and FH-Svartor in the literature. ClinVar contains an entry for this variant (Variation ID: 161269). For these reasons, this variant has been classified as Pathogenic.
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000238369 SCV000599322 pathogenic Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter curation
Color RCV000775030 SCV000909127 pathogenic Familial hypercholesterolemias 2018-08-26 criteria provided, single submitter clinical testing Pathogenic variant based on current evidence: This variant changes a single nucleotide in exon 3 of the LDLR gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in over 20 Norwegian individuals affected with familial hypercholesterolemia and is considered a founder mutation in that population (PMID: 7718019). This variant has also been reported in affected individuals in UK, Sweden, Netherlands and New Zealand (PMID: 9259195, 9698020, 11857755, 28964736). This variant is rare in the general population and has been identified in 1/246256 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of LDLR function is a known mechanism of disease. Based on available evidence, this variant is classified as Pathogenic.
CSER_CC_NCGL; University of Washington Medical Center RCV000148574 SCV000190287 pathogenic Hypercholesterolaemia 2014-06-01 no assertion criteria provided research
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000238369 SCV000606066 pathogenic Familial hypercholesterolemia no assertion criteria provided research

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