ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.694+1G>A

dbSNP: rs879254646
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237423 SCV000294917 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Color Diagnostics, LLC DBA Color Health RCV000775047 SCV000909145 likely pathogenic Familial hypercholesterolemia 2019-03-12 criteria provided, single submitter clinical testing This variant changes a single nucleotide in intron 4 canonical splice donor site of the LDLR gene. This variant is predicted to cause aberrant splicing and likely results in an absent or disrupted protein product. RNA studies have not been performed for this variant. This variant has been reported in two individuals affected with familial hypercholesterolemia (PMID: 16542394). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of LDLR function is a known mechanism of disease. Based on available evidence, this variant is classified as Likely Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000775047 SCV001205282 pathogenic Familial hypercholesterolemia 2025-01-14 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 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). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with familial hypercholesterolemia (PMID: 15199436, 16542394; internal data). ClinVar contains an entry for this variant (Variation ID: 251402). 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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