Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9117 | 27574;27575;27576 | chr2:178712573;178712572;178712571 | chr2:179577300;179577299;179577298 |
| N2AB | 8800 | 26623;26624;26625 | chr2:178712573;178712572;178712571 | chr2:179577300;179577299;179577298 |
| N2A | 7873 | 23842;23843;23844 | chr2:178712573;178712572;178712571 | chr2:179577300;179577299;179577298 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | None | 0.152 | None | N | 0.135 | 0.142 | 0.104622674875 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.63E-05 | None | 0 | None | 0 | 0 | 0 |
| R/K | None | 0.152 | None | N | 0.135 | 0.142 | 0.104622674875 | gnomAD-4.0.0 | 1.36963E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.04312E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/M | rs375907742  |
-0.054 | 0.741 | N | 0.377 | 0.273 | 0.366466682447 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 6.52E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/M | rs375907742 |
-0.054 | 0.741 | N | 0.377 | 0.273 | 0.366466682447 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/M | rs375907742 |
-0.054 | 0.741 | N | 0.377 | 0.273 | 0.366466682447 | gnomAD-4.0.0 | 1.24041E-06 | None | None | None | None | I | None | 2.67301E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | None | None | 0.027 | N | 0.373 | 0.213 | 0.254761474806 | gnomAD-4.0.0 | 1.59463E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86413E-06 | 0 | 0 |
| R/T | rs375907742 |
0.251 | 0.002 | N | 0.212 | 0.187 | None | gnomAD-2.1.1 | 6.11E-05 | None | None | None | None | I | None | 0 | 3.70518E-04 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 2.83607E-04 |
| R/T | rs375907742 |
0.251 | 0.002 | N | 0.212 | 0.187 | None | gnomAD-3.1.2 | 6.57E-05 | None | None | None | None | I | None | 0 | 3.27654E-04 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 4.78469E-04 |
| R/T | rs375907742 |
0.251 | 0.002 | N | 0.212 | 0.187 | None | gnomAD-4.0.0 | 2.23274E-05 | None | None | None | None | I | None | 0 | 3.34225E-04 | None | 0 | 0 | None | 0 | 0 | 1.27215E-05 | 0 | 1.60292E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2371 | likely_benign | 0.2211 | benign | -0.792 | Destabilizing | 0.035 | N | 0.375 | neutral | None | None | None | None | I |
| R/C | 0.2135 | likely_benign | 0.1867 | benign | -0.741 | Destabilizing | 0.935 | D | 0.343 | neutral | None | None | None | None | I |
| R/D | 0.5198 | ambiguous | 0.5091 | ambiguous | 0.138 | Stabilizing | 0.149 | N | 0.393 | neutral | None | None | None | None | I |
| R/E | 0.2244 | likely_benign | 0.2261 | benign | 0.266 | Stabilizing | 0.035 | N | 0.343 | neutral | None | None | None | None | I |
| R/F | 0.431 | ambiguous | 0.3891 | ambiguous | -0.662 | Destabilizing | 0.791 | D | 0.361 | neutral | None | None | None | None | I |
| R/G | 0.1463 | likely_benign | 0.1297 | benign | -1.085 | Destabilizing | 0.117 | N | 0.406 | neutral | N | 0.440976102 | None | None | I |
| R/H | 0.1087 | likely_benign | 0.1054 | benign | -1.361 | Destabilizing | 0.555 | D | 0.413 | neutral | None | None | None | None | I |
| R/I | 0.1905 | likely_benign | 0.1759 | benign | -0.008 | Destabilizing | 0.38 | N | 0.371 | neutral | None | None | None | None | I |
| R/K | 0.0592 | likely_benign | 0.063 | benign | -0.598 | Destabilizing | None | N | 0.135 | neutral | N | 0.32730388 | None | None | I |
| R/L | 0.1669 | likely_benign | 0.1582 | benign | -0.008 | Destabilizing | 0.149 | N | 0.386 | neutral | None | None | None | None | I |
| R/M | 0.1493 | likely_benign | 0.1407 | benign | -0.392 | Destabilizing | 0.741 | D | 0.377 | neutral | N | 0.500312408 | None | None | I |
| R/N | 0.3506 | ambiguous | 0.3342 | benign | -0.184 | Destabilizing | 0.149 | N | 0.337 | neutral | None | None | None | None | I |
| R/P | 0.2527 | likely_benign | 0.2276 | benign | -0.249 | Destabilizing | 0.555 | D | 0.349 | neutral | None | None | None | None | I |
| R/Q | 0.0867 | likely_benign | 0.0874 | benign | -0.326 | Destabilizing | 0.081 | N | 0.382 | neutral | None | None | None | None | I |
| R/S | 0.2869 | likely_benign | 0.2781 | benign | -0.985 | Destabilizing | 0.027 | N | 0.373 | neutral | N | 0.456174841 | None | None | I |
| R/T | 0.15 | likely_benign | 0.1445 | benign | -0.671 | Destabilizing | 0.002 | N | 0.212 | neutral | N | 0.418733961 | None | None | I |
| R/V | 0.2473 | likely_benign | 0.2375 | benign | -0.249 | Destabilizing | 0.149 | N | 0.415 | neutral | None | None | None | None | I |
| R/W | 0.1842 | likely_benign | 0.1674 | benign | -0.356 | Destabilizing | 0.915 | D | 0.368 | neutral | N | 0.500659124 | None | None | I |
| R/Y | 0.3288 | likely_benign | 0.2993 | benign | -0.062 | Destabilizing | 0.555 | D | 0.384 | 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.