Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32018 | 96277;96278;96279 | chr2:178544092;178544091;178544090 | chr2:179408819;179408818;179408817 |
| N2AB | 30377 | 91354;91355;91356 | chr2:178544092;178544091;178544090 | chr2:179408819;179408818;179408817 |
| N2A | 29450 | 88573;88574;88575 | chr2:178544092;178544091;178544090 | chr2:179408819;179408818;179408817 |
| N2B | 22953 | 69082;69083;69084 | chr2:178544092;178544091;178544090 | chr2:179408819;179408818;179408817 |
| Novex-1 | 23078 | 69457;69458;69459 | chr2:178544092;178544091;178544090 | chr2:179408819;179408818;179408817 |
| Novex-2 | 23145 | 69658;69659;69660 | chr2:178544092;178544091;178544090 | chr2:179408819;179408818;179408817 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs773714477  |
None | 0.046 | N | 0.352 | 0.044 | 0.183819452728 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/E | rs773714477 |
None | 0.046 | N | 0.352 | 0.044 | 0.183819452728 | gnomAD-4.0.0 | 4.96988E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.79737E-06 | 0 | 0 |
| D/H | rs1275646531 |
-0.833 | 0.998 | N | 0.743 | 0.356 | 0.426551566703 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.42674E-04 | None | 0 | None | 0 | 0 | 0 |
| D/H | rs1275646531 |
-0.833 | 0.998 | N | 0.743 | 0.356 | 0.426551566703 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92604E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | rs1275646531 |
-0.833 | 0.998 | N | 0.743 | 0.356 | 0.426551566703 | gnomAD-4.0.0 | 6.57246E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.92604E-04 | None | 0 | 0 | 0 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1779 | likely_benign | 0.1468 | benign | -0.069 | Destabilizing | 0.939 | D | 0.687 | prob.neutral | N | 0.3307254 | None | None | N |
| D/C | 0.7127 | likely_pathogenic | 0.626 | pathogenic | -0.003 | Destabilizing | 0.999 | D | 0.769 | deleterious | None | None | None | None | N |
| D/E | 0.1254 | likely_benign | 0.1058 | benign | -0.167 | Destabilizing | 0.046 | N | 0.352 | neutral | N | 0.42817459 | None | None | N |
| D/F | 0.7109 | likely_pathogenic | 0.6212 | pathogenic | -0.163 | Destabilizing | 0.999 | D | 0.787 | deleterious | None | None | None | None | N |
| D/G | 0.2133 | likely_benign | 0.1772 | benign | -0.206 | Destabilizing | 0.939 | D | 0.695 | prob.neutral | N | 0.448589934 | None | None | N |
| D/H | 0.4107 | ambiguous | 0.3419 | ambiguous | 0.267 | Stabilizing | 0.998 | D | 0.743 | deleterious | N | 0.486281531 | None | None | N |
| D/I | 0.4515 | ambiguous | 0.3685 | ambiguous | 0.227 | Stabilizing | 0.993 | D | 0.801 | deleterious | None | None | None | None | N |
| D/K | 0.4436 | ambiguous | 0.3564 | ambiguous | 0.371 | Stabilizing | 0.91 | D | 0.693 | prob.neutral | None | None | None | None | N |
| D/L | 0.4732 | ambiguous | 0.3816 | ambiguous | 0.227 | Stabilizing | 0.986 | D | 0.776 | deleterious | None | None | None | None | N |
| D/M | 0.6487 | likely_pathogenic | 0.5695 | pathogenic | 0.161 | Stabilizing | 0.999 | D | 0.779 | deleterious | None | None | None | None | N |
| D/N | 0.1462 | likely_benign | 0.1244 | benign | 0.247 | Stabilizing | 0.939 | D | 0.687 | prob.neutral | N | 0.485588097 | None | None | N |
| D/P | 0.5637 | ambiguous | 0.5017 | ambiguous | 0.148 | Stabilizing | 0.993 | D | 0.771 | deleterious | None | None | None | None | N |
| D/Q | 0.3984 | ambiguous | 0.3337 | benign | 0.243 | Stabilizing | 0.647 | D | 0.426 | neutral | None | None | None | None | N |
| D/R | 0.5081 | ambiguous | 0.4325 | ambiguous | 0.575 | Stabilizing | 0.986 | D | 0.747 | deleterious | None | None | None | None | N |
| D/S | 0.1495 | likely_benign | 0.1253 | benign | 0.102 | Stabilizing | 0.953 | D | 0.659 | neutral | None | None | None | None | N |
| D/T | 0.297 | likely_benign | 0.2464 | benign | 0.204 | Stabilizing | 0.986 | D | 0.739 | prob.delet. | None | None | None | None | N |
| D/V | 0.2649 | likely_benign | 0.2125 | benign | 0.148 | Stabilizing | 0.991 | D | 0.776 | deleterious | N | 0.485761456 | None | None | N |
| D/W | 0.8976 | likely_pathogenic | 0.8633 | pathogenic | -0.111 | Destabilizing | 0.999 | D | 0.752 | deleterious | None | None | None | None | N |
| D/Y | 0.3233 | likely_benign | 0.2624 | benign | 0.06 | Stabilizing | 0.997 | D | 0.791 | deleterious | N | 0.486454889 | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.