ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.2585T>C (p.Val862Ala) (rs145142090)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Integrative and Experimental Genomics,University of Luebeck RCV000172972 SCV000212150 likely benign Familial hypercholesterolemia 1 criteria provided, single submitter research
Invitae RCV000468217 SCV000541937 uncertain significance Familial hypercholesterolemia 2; Hypobetalipoproteinemia, familial, 1 2016-04-16 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 862 of the APOB protein (p.Val862Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. This variant is present in population databases (rs145142090, ExAC <0.01%). This variant was reported in a family affected with premature myocardial infarction but it did not segregate with the disease (PMID: 26036859). ClinVar contains an entry for this variant (Variation ID: 189305). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000172972 SCV000687218 uncertain significance Familial hypercholesterolemia 1 2017-10-06 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant is a missense variant located in the beta alpha 1 domain of the APOB protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant 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 was reported in a family affected with premature myocardial infarction but it did not segregate with elevated LDL-C (PMID: 26036859). This variant has been identified in 2/66732 non-Finnish European chromosomes by the Exome Aggregation Consortium (ExAC) general population database.
Color RCV000775217 SCV000909461 uncertain significance Familial hypercholesterolemia 2018-05-16 criteria provided, single submitter clinical testing Variant of Uncertain Significance based on current evidence: This missense variant (also known as p.Val835Ala in the mature protein) is located in the beta alpha 1 domain of the APOB protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant 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 was reported in a family affected with premature myocardial infarction but it did not segregate with elevated LDL-C levels (PMID: 26036859). This variant has been identified in 4/246152 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.

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