ClinVar Miner

Submissions for variant NM_001195800.2(LDLR):c.314-2019del (rs1057516135)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Robarts Research Institute,Western University RCV000408765 SCV000484809 likely pathogenic Familial hypercholesterolemia 1 criteria provided, single submitter clinical testing
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV000408765 SCV000839989 pathogenic Familial hypercholesterolemia 1 2017-05-24 criteria provided, single submitter clinical testing The c.467del (p.Asn156Thrfs*50) variant in the LDLR gene has not been reported in the ExAC database not has been observed in our internal database. This variant has been reported in ClinVar as a likely pathogenic variant (RCV000408765.1) based on a publication [PMID 27765764] . However, the variant was not observed in this report and it is thus considered a novel variant by our criteria. This 1 bp deletion in exon 4 results in a frameshift and the creation of a premature stop codon, 50 amino acid downstream of Asn156. This variant is predicted to result in a loss of function of the protein. This variant is thus classified as pathogenic.
GeneDx RCV001008350 SCV001168118 likely pathogenic not provided 2018-09-20 criteria provided, single submitter clinical testing Although the c.467delA likely pathogenic variant in the LDLR gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon asparagine 156, changing it to a threonine, and creating a premature stop codon at position 50 of the new reading frame, denoted p.Asn156ThrfsX50. This variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift variants in the LDLR gene have been reported in Human Gene Mutation Database in association with FH (Stenson et al., 2014), and loss of function is a mechanism of disease for this gene. Furthermore, the c.467delA variant has not been observed in large population cohorts (Lek et al., 2016).
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000408765 SCV000606130 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research

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