ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.10708C>T (p.His3570Tyr) (rs201736972)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766982 SCV000589625 uncertain significance not provided 2018-07-19 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the APOB gene. The H3570Y variant has been previously reported in association with familial hypercholesterolemia and coronary heart disease (Soufi et al., 2004; Liyanage et al., 2008; Galaska et al., 2016). The H3570Y variant is observed in 18/66660 (0.03%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The H3570Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000498755 SCV000711795 uncertain significance not specified 2018-12-07 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Color RCV000775453 SCV000909816 uncertain significance Familial hypercholesterolemias 2018-06-06 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant (also known as p.His3543Tyr 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. To our knowledge, functional assays have not been performed for this variant. While this variant has been reported in a Polish individual affected with familial hypercholesterolemia (PMID: 26666465) and German individuals affected with coronary heart disease (PMID: 15135245), it has also been identified in 36/276614 chromosomes in the general population (33/126240 non-Finnish European chromosomes) by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000508757 SCV000605960 pathogenic Familial hypercholesterolemia no assertion criteria provided research

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