ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1846-1G>T

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003742271 SCV004457543 pathogenic Familial hypercholesterolemia 2023-04-22 criteria provided, single submitter clinical testing Disruption of this splice site has been observed in individuals with hypercholesterolemia (PMID: 8828981, 11317362, 11737238, 15359125, 16542394, 20828696). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 12 of the LDLR gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

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