Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17357 | 52294;52295;52296 | chr2:178609241;178609240;178609239 | chr2:179473968;179473967;179473966 |
| N2AB | 15716 | 47371;47372;47373 | chr2:178609241;178609240;178609239 | chr2:179473968;179473967;179473966 |
| N2A | 14789 | 44590;44591;44592 | chr2:178609241;178609240;178609239 | chr2:179473968;179473967;179473966 |
| N2B | 8292 | 25099;25100;25101 | chr2:178609241;178609240;178609239 | chr2:179473968;179473967;179473966 |
| Novex-1 | 8417 | 25474;25475;25476 | chr2:178609241;178609240;178609239 | chr2:179473968;179473967;179473966 |
| Novex-2 | 8484 | 25675;25676;25677 | chr2:178609241;178609240;178609239 | chr2:179473968;179473967;179473966 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 0.171 | N | 0.377 | 0.11 | 0.0884992946249 | gnomAD-4.0.0 | 2.91106E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.72681E-06 | 0 | 0 |
| I/V | rs773768518  |
0.027 | None | N | 0.111 | 0.252 | 0.18995819373 | gnomAD-2.1.1 | 5.6E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.15E-05 | 0 |
| I/V | rs773768518 |
0.027 | None | N | 0.111 | 0.252 | 0.18995819373 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs773768518 |
0.027 | None | N | 0.111 | 0.252 | 0.18995819373 | gnomAD-4.0.0 | 3.92652E-06 | None | None | None | None | I | None | 1.39032E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.37777E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1375 | likely_benign | 0.1361 | benign | -0.696 | Destabilizing | 0.007 | N | 0.276 | neutral | None | None | None | None | I |
| I/C | 0.4269 | ambiguous | 0.4233 | ambiguous | -0.701 | Destabilizing | 0.356 | N | 0.443 | neutral | None | None | None | None | I |
| I/D | 0.3849 | ambiguous | 0.3786 | ambiguous | -0.287 | Destabilizing | 0.072 | N | 0.563 | neutral | None | None | None | None | I |
| I/E | 0.25 | likely_benign | 0.254 | benign | -0.375 | Destabilizing | 0.072 | N | 0.551 | neutral | None | None | None | None | I |
| I/F | 0.1033 | likely_benign | 0.1016 | benign | -0.682 | Destabilizing | None | N | 0.127 | neutral | N | 0.425641291 | None | None | I |
| I/G | 0.3879 | ambiguous | 0.3842 | ambiguous | -0.865 | Destabilizing | 0.031 | N | 0.512 | neutral | None | None | None | None | I |
| I/H | 0.2716 | likely_benign | 0.2706 | benign | -0.124 | Destabilizing | 0.628 | D | 0.495 | neutral | None | None | None | None | I |
| I/K | 0.1854 | likely_benign | 0.1803 | benign | -0.44 | Destabilizing | 0.072 | N | 0.539 | neutral | None | None | None | None | I |
| I/L | 0.1024 | likely_benign | 0.1067 | benign | -0.371 | Destabilizing | None | N | 0.119 | neutral | N | 0.462466095 | None | None | I |
| I/M | 0.0759 | likely_benign | 0.0801 | benign | -0.469 | Destabilizing | 0.171 | N | 0.377 | neutral | N | 0.492442286 | None | None | I |
| I/N | 0.1451 | likely_benign | 0.1378 | benign | -0.242 | Destabilizing | 0.055 | N | 0.59 | neutral | N | 0.46194602 | None | None | I |
| I/P | 0.7402 | likely_pathogenic | 0.7082 | pathogenic | -0.447 | Destabilizing | 0.136 | N | 0.553 | neutral | None | None | None | None | I |
| I/Q | 0.2209 | likely_benign | 0.2234 | benign | -0.468 | Destabilizing | 0.356 | N | 0.535 | neutral | None | None | None | None | I |
| I/R | 0.1607 | likely_benign | 0.153 | benign | 0.133 | Stabilizing | 0.072 | N | 0.551 | neutral | None | None | None | None | I |
| I/S | 0.1244 | likely_benign | 0.1153 | benign | -0.691 | Destabilizing | 0.001 | N | 0.242 | neutral | N | 0.373382886 | None | None | I |
| I/T | 0.083 | likely_benign | 0.0778 | benign | -0.669 | Destabilizing | None | N | 0.147 | neutral | N | 0.374692395 | None | None | I |
| I/V | 0.0603 | likely_benign | 0.0641 | benign | -0.447 | Destabilizing | None | N | 0.111 | neutral | N | 0.462292737 | None | None | I |
| I/W | 0.5869 | likely_pathogenic | 0.5874 | pathogenic | -0.689 | Destabilizing | 0.864 | D | 0.493 | neutral | None | None | None | None | I |
| I/Y | 0.3355 | likely_benign | 0.3265 | benign | -0.448 | Destabilizing | 0.038 | N | 0.523 | neutral | None | None | None | None | I |
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.