ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.622G>T (p.Glu208Ter)

dbSNP: rs879254597
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237158 SCV000294828 pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Invitae RCV000586410 SCV000627044 pathogenic Familial hypercholesterolemia 2020-12-21 criteria provided, single submitter clinical testing This variant has been observed in individual(s) with familial hypercholesterolemia (PMID: 15199436). ClinVar contains an entry for this variant (Variation ID: 251329). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu208*) in the LDLR gene. It is expected to result in an absent or disrupted protein product.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586410 SCV000697243 likely pathogenic Familial hypercholesterolemia 2017-02-03 criteria provided, single submitter clinical testing Variant summary: The LDLR c.622G>T (p.Glu208X) variant, alternatively also known as E187X, results in a premature termination codon, predicted to cause a truncated or absent LDLR protein due to nonsense mediated decay (NMD), which are commonly known mechanisms for disease. If it escapes NMD, the variant is expected to truncate LDL receptor class A and B repeats, EGF-like domain, cysteine-rich domain and beta-propeller domain (InterPro). Truncations downstream of this position have been classified as pathogenic by our laboratory and others (e.g. p.Cys276X, p.Arg350X, p.Gln384X, etc.). This variant is absent in 120436 control chromosomes from ExAC. In literature, this variant is reported in one index patient with hypercholesterolemia (Leren_2004). Multiple databases have classified this variant as pathogenic. Taken together, this variant is classified as likely pathogenic.
Brunham Lab, Centre for Heart and Lung Innovation, University of British Columbia RCV000237158 SCV001432614 pathogenic Hypercholesterolemia, familial, 1 2019-06-04 criteria provided, single submitter research
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237158 SCV000606172 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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