ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.10519C>T (p.Arg3507Trp) (rs754264874)

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Total submissions: 2
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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 RCV000505233 SCV000599291 uncertain significance Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter curation
Color RCV000775458 SCV000909821 uncertain significance Familial hypercholesterolemia 2018-05-16 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant (also known as p.Arg3480Trp in the mature protein) is a missense variant located in the beta 2 domain of the APOB protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. Functional assay using LDL isolated from this subject showed partially defective binding to LDL receptor (PMID: 11115503). This variant has been reported in an individual with mild to moderate hypercholesterolemia (PMID: 11115503). This variant is rare in the general population and has been identified in 6/276360 chromosomes by the Genome Aggregation Database (gnomAD). Different variant occurring at the same amino acid, Arg3507Pro (Arg3480Pro in the mature protein), was associated with hypobetalipoproteinemia despite decreased binding to LDL receptor (PMID: 15797858). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.

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