Submissions for variant NM_000384.3(APOB):c.631C>T (p.Gln211Ter)

dbSNP: rs143301836

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000218762	SCV000271205	likely pathogenic	Hypobetalipoproteinemia	2015-08-25	criteria provided, single submitter	clinical testing	The p.Gln211X variant in APOB has not been previously reported in individuals wi th hypobetalipoproteinemia or in large population studies. This nonsense variant leads to a premature termination codon at position 211, which is predicted to l ead to a truncated or absent protein. Heterozygous loss-of-function of the APOB gene has been associated with familial hypobetalipoproteinemia (Welty 2014, Burn ett 2015). In summary, although additional studies are required to fully establi sh its clinical significance, the p.Gln211X variant is likely pathogenic for hyp obetalipoproteinemia.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001248959	SCV001422755	likely pathogenic	Familial hypobetalipoproteinemia 1	2020-01-22	criteria provided, single submitter	curation	The p.Gln211Ter variant in APOB has not been previously reported in individuals with familial low LDL and was absent from large population studies. This variant has been reported in ClinVar (VariationID: 228245) as likely pathogenic by the Laboratory for Molecular Medicine. This nonsense variant leads to a premature termination codon at position 211, which is predicted to lead to a truncated or absent protein. Loss of function of the APOB gene is an established disease mechanism in autosomal recessive low LDL. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1, PM2 (Richards 2015).