ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1200C>A (p.Tyr400Ter)

dbSNP: rs879254827
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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 RCV000237899 SCV000295292 pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Fundacion Hipercolesterolemia Familiar RCV000237899 SCV000607573 pathogenic Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research
Color Diagnostics, LLC DBA Color Health RCV000775059 SCV000909160 pathogenic Familial hypercholesterolemia 2022-11-16 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 9 of the EGF precursor homology domain of the LDLR gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with familial hypercholesterolemia (PMID: 15241806, 16250003, 18096825). It has also been reported in an individual suspected to be affected with familial hypercholesterolemia (PMID: 34037665). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of LDLR function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000775059 SCV000941734 pathogenic Familial hypercholesterolemia 2023-09-18 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 251728). This variant is also known as p.Y379X. This premature translational stop signal has been observed in individuals with familial hypercholesterolemia (PMID: 15241806, 16250003, 18096825; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr400*) 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).
Ambry Genetics RCV004992122 SCV005609289 pathogenic Cardiovascular phenotype 2024-11-15 criteria provided, single submitter clinical testing The p.Y400* pathogenic mutation (also known as c.1200C>A), located in coding exon 9 of the LDLR gene, results from a C to A substitution at nucleotide position 1200. This changes the amino acid from a tyrosine to a stop codon within coding exon 9. This variant (also referred to as p.Y379X) was reported in multiple individuals with features consistent with familial hypercholesterolemia (Mozas P et al. Hum Mutat, 2004 Aug;24:187; Fouchier SW et al. Hum Mutat, 2005 Dec;26:550-6; Marco-Benedí V et al. Atherosclerosis, 2022 May;349:211-218). 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 RCV000237899 SCV000606355 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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