Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28997 | 87214;87215;87216 | chr2:178558470;178558469;178558468 | chr2:179423197;179423196;179423195 |
| N2AB | 27356 | 82291;82292;82293 | chr2:178558470;178558469;178558468 | chr2:179423197;179423196;179423195 |
| N2A | 26429 | 79510;79511;79512 | chr2:178558470;178558469;178558468 | chr2:179423197;179423196;179423195 |
| N2B | 19932 | 60019;60020;60021 | chr2:178558470;178558469;178558468 | chr2:179423197;179423196;179423195 |
| Novex-1 | 20057 | 60394;60395;60396 | chr2:178558470;178558469;178558468 | chr2:179423197;179423196;179423195 |
| Novex-2 | 20124 | 60595;60596;60597 | chr2:178558470;178558469;178558468 | chr2:179423197;179423196;179423195 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/L | rs751293680  |
0.172 | 0.027 | N | 0.335 | 0.158 | 0.480123561213 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| S/L | rs751293680 |
0.172 | 0.027 | N | 0.335 | 0.158 | 0.480123561213 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/L | rs751293680 |
0.172 | 0.027 | N | 0.335 | 0.158 | 0.480123561213 | gnomAD-4.0.0 | 3.84326E-06 | None | None | None | None | N | None | 1.6913E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78563E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0672 | likely_benign | 0.0671 | benign | -0.628 | Destabilizing | None | N | 0.08 | neutral | N | 0.438212651 | None | None | N |
| S/C | 0.102 | likely_benign | 0.1024 | benign | -0.373 | Destabilizing | 0.555 | D | 0.347 | neutral | None | None | None | None | N |
| S/D | 0.2707 | likely_benign | 0.3133 | benign | -0.002 | Destabilizing | 0.149 | N | 0.293 | neutral | None | None | None | None | N |
| S/E | 0.3895 | ambiguous | 0.459 | ambiguous | 0.036 | Stabilizing | 0.149 | N | 0.259 | neutral | None | None | None | None | N |
| S/F | 0.1492 | likely_benign | 0.1435 | benign | -0.855 | Destabilizing | 0.001 | N | 0.228 | neutral | None | None | None | None | N |
| S/G | 0.0689 | likely_benign | 0.0672 | benign | -0.881 | Destabilizing | 0.035 | N | 0.291 | neutral | None | None | None | None | N |
| S/H | 0.2386 | likely_benign | 0.2688 | benign | -1.113 | Destabilizing | 0.791 | D | 0.353 | neutral | None | None | None | None | N |
| S/I | 0.1312 | likely_benign | 0.1293 | benign | -0.053 | Destabilizing | 0.081 | N | 0.362 | neutral | None | None | None | None | N |
| S/K | 0.4723 | ambiguous | 0.5589 | ambiguous | -0.4 | Destabilizing | 0.149 | N | 0.255 | neutral | None | None | None | None | N |
| S/L | 0.0836 | likely_benign | 0.0861 | benign | -0.053 | Destabilizing | 0.027 | N | 0.335 | neutral | N | 0.500570619 | None | None | N |
| S/M | 0.117 | likely_benign | 0.1181 | benign | -0.119 | Destabilizing | 0.555 | D | 0.359 | neutral | None | None | None | None | N |
| S/N | 0.0825 | likely_benign | 0.0807 | benign | -0.489 | Destabilizing | 0.149 | N | 0.356 | neutral | None | None | None | None | N |
| S/P | 0.278 | likely_benign | 0.3631 | ambiguous | -0.211 | Destabilizing | 0.317 | N | 0.369 | neutral | D | 0.524330126 | None | None | N |
| S/Q | 0.3236 | likely_benign | 0.381 | ambiguous | -0.487 | Destabilizing | 0.555 | D | 0.382 | neutral | None | None | None | None | N |
| S/R | 0.466 | ambiguous | 0.548 | ambiguous | -0.341 | Destabilizing | 0.38 | N | 0.383 | neutral | None | None | None | None | N |
| S/T | 0.0638 | likely_benign | 0.0614 | benign | -0.471 | Destabilizing | None | N | 0.083 | neutral | N | 0.436785712 | None | None | N |
| S/V | 0.1189 | likely_benign | 0.1205 | benign | -0.211 | Destabilizing | 0.035 | N | 0.349 | neutral | None | None | None | None | N |
| S/W | 0.3062 | likely_benign | 0.321 | benign | -0.944 | Destabilizing | 0.935 | D | 0.404 | neutral | None | None | None | None | N |
| S/Y | 0.1507 | likely_benign | 0.1517 | benign | -0.604 | Destabilizing | 0.235 | N | 0.379 | 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.