ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.564C>A (p.Tyr188Ter)

dbSNP: rs121908034
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237391 SCV000294794 pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Fundacion Hipercolesterolemia Familiar RCV000237391 SCV000607474 pathogenic Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001854888 SCV002204407 pathogenic Familial hypercholesterolemia 2021-02-11 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This nonsense change has been observed in individual(s) with familial hypercholesterolemia (PMID: 10422803, 1734722). It has also been observed to segregate with disease in related individuals. This nonsense change is also known as Tyr167stop. ClinVar contains an entry for this variant (Variation ID: 251299). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr188*) 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 RCV002347938 SCV002652949 pathogenic Cardiovascular phenotype 2020-02-13 criteria provided, single submitter clinical testing The p.Y188* variant (also known as c.564C>A and p.Y167X), located in coding exon 4 of the LDLR gene, results from a C to A substitution at nucleotide position 564. This changes the amino acid from a tyrosine to a stop codon within coding exon 4. This variant has been reported in multiple individuals with a personal and family history of hypercholesterolemia, both as a heterozygous and homozygous variant (Taylor A et al. Clin. Genet., 2007 Jun;71:561-8, Landsberger D et al. Am. J. Hum. Genet., 1992 Feb;50:427-33, Ekström U et al. Clin. Genet., 1999 May;55:332-9). 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.

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