Table 3.
Methods used by each study for identification and evaluation of CH variants.
| References | Sequencing technology | How CH variant identified | Post sequencing pathogenicity evaluation criteria |
|---|---|---|---|
| Maciaszek et al. (2019) | WGS | Mendelian inheritance | ACMG/AMP guidelines |
| Schieffer et al. (2019) | WES; Sanger | Mendelian inheritance | ACMG/AMP guidelines |
| Zhang et al. (2018) | WGS | Mendelian inheritance | SIFT; PolyPhen-2; MutationTaster (Schwarz et al., 2014), M-CAP; and AMP/ACMG guidelines |
| Diness et al. (2018) | WES | Mendelian inheritance | CADD (Kircher et al., 2014); gene expression analysis |
| Sharapova et al. (2018) | Sanger | Mendelian inheritance | PolyPhen-2 |
| Waszak et al. (2018) | WGS; WES; RNA-seq | Multiple sites within the same gene were phased with paired-end RNA sequencing data and individual sites were merged to calculate haplotype-specific expression ratios. | ClinVar |
| Diets et al. (2018) | WES | Mendelian inheritance | SIFT; PolyPhen2; CADD |
| Gröbner et al. (2018) | WGS; WES | Used Platypus which is a haplotype-based variant caller (Rimmer et al., 2014) | CADD; Mutation Assessor (Reva et al., 2011) |
| Salih et al. (2018) | Sanger (inferred) | Mendelian inheritance | – |
| Moriyama et al. (2017) | Sanger | PHASE was used to infer haplotypes (Stephens and Scheet, 2005) | – |
| Svojgr et al. (2016) | SNP-array | Mendelian inheritance | – |
| Piane et al. (2016) | Sanger | Mendelian inheritance | SIFT; Polyphen; MutationTaster |
| Spinella et al. (2015) | WES | Mendelian inheritance | SIFT; PolyPhen-2; and hidden Markov models |
| Zhang et al. (2015) | WGS; WES; RNA-seq | Used RNA-seq data to determine CH nature of variant | ACMG/AMP guidelines; genetic database; medical literature; computational predictions; and second hits identified in the tumor genome |
| Valentine et al. (2014) | WES | Mendelian inheritance | Filtered for functional consequences (e.g., non-synonymous and coding) |
| Bakry et al. (2014) | Sanger | Mendelian inheritance | Algorithms to predict RNA/protein disruption |
| Chmara et al. (2013) | Direct sequencing; MLPA | Mendelian inheritance | – |
| Herkert et al. (2011) | Direct sequencing; MLPA | Mendelian inheritance | SIFT; AlignGVGD (Tavtigian et al., 2008); PolyPhen-2; and RNA splice site prediction programs |
| Leenen et al. (2011) | Sanger | Mendelian inheritance | Literature search |
| Majumdar et al. (2010) | Sanger (inferred) | Mendelian inheritance | – |
| Peters et al. (2009) | Sanger (inferred) | Mendelian inheritance | – |
| Scott et al. (2007) | Sanger | Mendelian inheritance | Literature search |
| Okkels et al. (2006) | Sanger | Mendelian inheritance | – |
| Østergaard et al. (2005) | Sanger | Mendelian inheritance | – |
| De Rosa et al. (2000) | Sanger | Mendelian inheritance | – |
| Quesnel et al. (1999) | Sanger | Mendelian inheritance | mRNA assay |
A value of “–” indicates that no clear description was provided by the authors. WGS, whole genome sequencing; WES, whole exome sequencing; MLPA, Multiplex Ligation-dependent Probe Amplification.