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Table 1 Heterozygous rare variants detected in atypical hypobetalipoproteinemia proband

From: Complex genetic architecture in severe hypobetalipoproteinemia

gene/chr exon cDNA change amino acid ExAC MAF(A) CADD SIFT PolyPhen-2 comments
APOB/2p24 10 c.T1223C p.I408T 0.0268 15.7 0.211 0.065 uncommon missense variant; possibly pathogenic [17]
  26 c.G6895C p.D2299H 0.0215 19.6 0.062 0.98 uncommon missense variant; possibly pathogenic [17]
  26 c.A7242C p.E2414D 0.0076 11 0.405 0.007 uncommon missense variant; unlikely pathogenic
  29 c.T12803C p.M4268T 0.0076 0.001 0.485 0 uncommon missense variant; unlikely pathogenic [17]
MTTP/4q23 13 c.G1769T p.S590I NP 28.5 0.034 0.996 very rare proven dysfunctional variant [7, 9]
PCSK9/1p32 8 c.G1327A p.A443T 0.0981 9.68 0.534 0.004 variant of unknown significance
SAR1B/5q31 5 c.A314G p.H105R NP 9.84 1 0 variant of unknown significance
ANGPTL3/1p31 4 c.T776C p.M259T 0.0542 3.46 0.084 0.001 variant of unknown significance
  1. Abbreviations: chr Chromosomal locus, cDNA Coding DNA sequence, APOB Gene encoding apolipoprotein B, MTTP Gene encoding microsomal triglyceride transfer protein, PCSK9, Gene encoding proprotein convertase subtilisin kexin 9, SAR1B Gene encoding S. cerevisiae homolog B (chylomicron retention disease gene), ANGPTL3 Gene encoding angiopoietin-like protein 3, ExAC Exome aggregation consortium [18] (url: http://exac.broadinstitute.org/), MAF(A) Minor allele frequency in African populations, NP Not present in database, CADD Combined annotation dependent depletion algorithm [5] (url: http://cadd.gs.washington.edu/), SIFT Sorting intolerant from tolerant algorithm [6] (url: http://sift.jcvi.org/), PolyPhen-2 Polymorphism phenotyping tool version 2 [19] (url: http://genetics.bwh.harvard.edu/pph2/)
  2. Explanation of predictive functional scores: A CADD score > 20 is predicted to be in the top 1% of most deleterious substitutions within the human genome. A CADD score from 10 to 20 is predicted to be in the top 10% of most deleterious substitutions within the human genome. A SIFT score ≤ 0.05 is considered to be ‘deleterious’; while a score ≥ 0.05 is considered to be ‘tolerated’. A PolyPhen-2 score of 0.957 to 1.0 is considered to be ‘probably damaging’; of 0.454 to 0.956 is considered to be ‘possibly damaging’ and of 0.0 to 0.453 is considered to be ‘benign’