ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1988-1G>A

dbSNP: rs1555807335
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge RCV000505181 SCV000599401 pathogenic Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter curation
Labcorp Genetics (formerly Invitae), Labcorp RCV003581673 SCV004297872 pathogenic Familial hypercholesterolemia 2022-12-05 criteria provided, single submitter clinical testing This variant disrupts a region of the LDLR protein in which other variant(s) (p.Cys667Tyr) have been determined to be pathogenic (PMID: 18263977, 23375686, 27765764). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. This sequence change affects an acceptor splice site in intron 13 of the LDLR gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with autosomal dominant familial hypercholesterolemia (PMID: 16792510). ClinVar contains an entry for this variant (Variation ID: 438329). Studies have shown that disruption of this splice site results in skipping of exon 14, but is expected to preserve the integrity of the reading-frame (PMID: 19208450).
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000505181 SCV000606568 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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