ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1640T>C (p.Leu547Pro) (rs879254968)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000775074 SCV000909176 uncertain significance Familial hypercholesterolemias 2018-08-28 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant (also known as p.Leu526Pro in the mature protein) is located in the fourth LDLR type B repeat of the EGF precursor homology domain of the LDLR protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in an individual affected with familial hypercholesterolemia and her affected father (PMID: 28161202). This variant is rare in the general population and has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Although available evidence suggests this variant may be associated with disease, additional studies are necessary to determine the pathogenicity of this variant conclusively.
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000238388 SCV000839984 likely pathogenic Familial hypercholesterolemia 2017-09-19 criteria provided, single submitter clinical testing This c.1640T>C (p.Leu547Pro) variant in the LDLR gene has been reported in multiple individuals with familial hypercholesterolemia and has been shown to segregate with affected status in one family (PMID: 22881376, 28161202). The c.1640T>C variant is not detected in the general population and leucine at position 547 of the LDLR protein is highly evolutionarily conserved. The c.1640T>C (p.Leu547Pro) variant in the LDLR gene is classified as likely pathogenic.
LDLR-LOVD, British Heart Foundation RCV000238388 SCV000295554 likely pathogenic Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter research

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