ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.409G>T (p.Glu137Ter) (rs766243954)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000470253 SCV000541929 pathogenic Hypobetalipoproteinemia, familial, 1 2016-10-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 137 (p.Glu137*) of the APOB gene. It is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in APOB are known to be pathogenic for hypobetalipoproteinemia (PMID: 20032471). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000763067 SCV000893570 pathogenic Familial hypercholesterolemia 2; Hypobetalipoproteinemia, familial, 1 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000763067 SCV001580099 pathogenic Familial hypercholesterolemia 2; Hypobetalipoproteinemia, familial, 1 2016-10-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 137 (p.Glu137*) of the APOB gene. It is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in APOB are known to be pathogenic for hypobetalipoproteinemia (PMID: 20032471). For these reasons, this variant has been classified as Pathogenic.
Broad Institute Rare Disease Group, Broad Institute RCV000470253 SCV001422761 likely pathogenic Hypobetalipoproteinemia, familial, 1 2020-01-22 no assertion criteria provided curation The p.Glu137Ter variant in APOB has not been previously reported in individuals with low LDL, but has been identified in 0.006483% (1/15424) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs766243954). This variant has also been reported in ClinVar (VariationID: 404400) as pathogenic by Invitae and Fulgent Genetics. This nonsense variant leads to a premature termination codon at position 137, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the APOB gene is an established disease mechanism in low LDL. In summary, while there is some suspicion for a pathogenic role, the clinical significance of the p.Glu137Ter variant is uncertain. ACMG/AMP Criteria applied: PVS1, PM2 (Richards 2015).

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