ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.1400C>G (p.Ala467Gly) (rs376602710)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000407185 SCV000427156 uncertain significance Familial hypercholesterolemia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000308528 SCV000427157 uncertain significance Familial hypobetalipoproteinemia 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000655097 SCV000777022 uncertain significance Hypercholesterolemia, autosomal dominant, type B; Hypobetalipoproteinemia, familial, 1 2018-09-14 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 467 of the APOB protein (p.Ala467Gly). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and glycine. This variant is present in population databases (rs376602710, ExAC 0.03%). This variant has not been reported in the literature in individuals with APOB-related disease. ClinVar contains an entry for this variant (Variation ID: 334172). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000775220 SCV000909464 uncertain significance Familial hypercholesterolemias 2018-10-01 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant (also known as p.Ala440Gly 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 nor has this variant been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 10/246126 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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