Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24073 | 72442;72443;72444 | chr2:178573915;178573914;178573913 | chr2:179438642;179438641;179438640 |
| N2AB | 22432 | 67519;67520;67521 | chr2:178573915;178573914;178573913 | chr2:179438642;179438641;179438640 |
| N2A | 21505 | 64738;64739;64740 | chr2:178573915;178573914;178573913 | chr2:179438642;179438641;179438640 |
| N2B | 15008 | 45247;45248;45249 | chr2:178573915;178573914;178573913 | chr2:179438642;179438641;179438640 |
| Novex-1 | 15133 | 45622;45623;45624 | chr2:178573915;178573914;178573913 | chr2:179438642;179438641;179438640 |
| Novex-2 | 15200 | 45823;45824;45825 | chr2:178573915;178573914;178573913 | chr2:179438642;179438641;179438640 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | None | None | 0.565 | N | 0.387 | 0.234 | 0.256793551483 | gnomAD-4.0.0 | 2.05464E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87406E-05 | 0 | 1.80045E-06 | 0 | 0 |
| T/R | rs753519331  |
0.218 | 0.949 | N | 0.402 | 0.203 | 0.257786959452 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.3107E-04 | None | 0 | 0 | 0 |
| T/R | rs753519331 |
0.218 | 0.949 | N | 0.402 | 0.203 | 0.257786959452 | gnomAD-4.0.0 | 6.84881E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16044E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1282 | likely_benign | 0.1291 | benign | -0.172 | Destabilizing | 0.008 | N | 0.217 | neutral | N | 0.509906886 | None | None | N |
| T/C | 0.5518 | ambiguous | 0.5613 | ambiguous | -0.282 | Destabilizing | 0.989 | D | 0.423 | neutral | None | None | None | None | N |
| T/D | 0.3661 | ambiguous | 0.3521 | ambiguous | 0.314 | Stabilizing | 0.923 | D | 0.366 | neutral | None | None | None | None | N |
| T/E | 0.4296 | ambiguous | 0.4331 | ambiguous | 0.237 | Stabilizing | 0.923 | D | 0.381 | neutral | None | None | None | None | N |
| T/F | 0.4095 | ambiguous | 0.4253 | ambiguous | -0.738 | Destabilizing | 0.858 | D | 0.527 | neutral | None | None | None | None | N |
| T/G | 0.2599 | likely_benign | 0.2455 | benign | -0.277 | Destabilizing | 0.633 | D | 0.447 | neutral | None | None | None | None | N |
| T/H | 0.3517 | ambiguous | 0.3475 | ambiguous | -0.508 | Destabilizing | 0.996 | D | 0.543 | neutral | None | None | None | None | N |
| T/I | 0.3778 | ambiguous | 0.402 | ambiguous | -0.021 | Destabilizing | 0.565 | D | 0.387 | neutral | N | 0.471011665 | None | None | N |
| T/K | 0.2624 | likely_benign | 0.2754 | benign | -0.222 | Destabilizing | 0.722 | D | 0.38 | neutral | N | 0.453533528 | None | None | N |
| T/L | 0.1699 | likely_benign | 0.1805 | benign | -0.021 | Destabilizing | 0.011 | N | 0.257 | neutral | None | None | None | None | N |
| T/M | 0.1295 | likely_benign | 0.1447 | benign | -0.028 | Destabilizing | 0.923 | D | 0.407 | neutral | None | None | None | None | N |
| T/N | 0.1174 | likely_benign | 0.1118 | benign | -0.065 | Destabilizing | 0.923 | D | 0.365 | neutral | None | None | None | None | N |
| T/P | 0.2467 | likely_benign | 0.2339 | benign | -0.044 | Destabilizing | 0.949 | D | 0.403 | neutral | N | 0.507194655 | None | None | N |
| T/Q | 0.326 | likely_benign | 0.3305 | benign | -0.244 | Destabilizing | 0.961 | D | 0.395 | neutral | None | None | None | None | N |
| T/R | 0.2377 | likely_benign | 0.2529 | benign | 0.014 | Stabilizing | 0.949 | D | 0.402 | neutral | N | 0.462846445 | None | None | N |
| T/S | 0.1097 | likely_benign | 0.1059 | benign | -0.262 | Destabilizing | 0.092 | N | 0.226 | neutral | N | 0.411913405 | None | None | N |
| T/V | 0.2881 | likely_benign | 0.2994 | benign | -0.044 | Destabilizing | 0.633 | D | 0.383 | neutral | None | None | None | None | N |
| T/W | 0.7217 | likely_pathogenic | 0.7414 | pathogenic | -0.801 | Destabilizing | 0.996 | D | 0.629 | neutral | None | None | None | None | N |
| T/Y | 0.4632 | ambiguous | 0.4743 | ambiguous | -0.48 | Destabilizing | 0.961 | D | 0.543 | neutral | None | None | 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.