Table 4.
Frameshift variants found in the Czech cohort. The column Proof of pathogenicity provides information on which the variant evaluation is based—“null” indicating that the variant probably results in no gene product, 'MP' indicates multiple published patients (including this study), while 'FP' signifies functional proof of variant impact with referenced articles containing such evidence. The resources are indicated in the References column, and articles containing functional proof are [17]. Numbers of patients and probands of our cohort are given in corresponding columns. # indicates previously published probands/patients of our cohort, and x in x# indicates the number of them. The variant c.726_777del included in this table comprises more than 20 bases but because it does not affect the whole exon, it was not included in the CNV subset (Table 6). On the other hand, the deletion c.1225_1249 + 19del was placed in the splicing variant table (Table 5) as it primarily disrupts mRNA splicing
| Variant cDNA | Variant protein | Proof of pathogenicity | ACMG evaluation | Number of probands | Number of patients | References |
|---|---|---|---|---|---|---|
| c.120_121del | p.(Gly41Argfs*16) | Null, MP, FP [17] | Pathogenic | 1# | 3# | [17, 18, 33, 36, 42, 47, 56] |
| c.151_152del | p.(Ser51Glnfs*6) | Null | Pathogenic | 1 | 2 | novel |
| c.160del | p.(Leu54Tyrfs*25) | Null | Pathogenic | 1# | 31# | [18] |
| c.305_317del | p.(Pro102Leufs*42) | Null, FP [17] | Pathogenic | 21# | 141# | [17] |
| c.600dup | p.(Lys201Glnfs*56) | Null, MP | Pathogenic | 1# | 21# | [12, 30, 36, 47, 64] |
| c.650del | p.(Gly217fs*15) | Null, MP | Pathogenic | 1# | 1# | [17, 53] |
| c.726_777del | p.(Leu243Serfs*19) | Null | Pathogenic | 1 | 7 | novel |
| c.795_796delGGinsT | p.(Trp265Cysfs*14) | Null | Pathogenic | 1 | 2 | novel |
| c.855_856del | p.(Arg286Profs*18) | Null | Pathogenic | 1# | 2# | [18] |
| c.1115del | p.(Gln372Argfs*25) | Null | Pathogenic | 1# | 21# | [17] |
| c.1283del | p.(Cys428Leufs*3) | Null, MP | Pathogenic | 1# | 1# | [17, 33] |
| c.1284_1285del | p.(Cys428Trpfs*44) | Null, MP | Pathogenic | 31# | 41# | [18] |
| c.1460_1466del | p.(Lys487Metfs*87) | Null | Pathogenic | 1 | 5 | novel |