Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14547 | 43864;43865;43866 | chr2:178632255;178632254;178632253 | chr2:179496982;179496981;179496980 |
| N2AB | 12906 | 38941;38942;38943 | chr2:178632255;178632254;178632253 | chr2:179496982;179496981;179496980 |
| N2A | 11979 | 36160;36161;36162 | chr2:178632255;178632254;178632253 | chr2:179496982;179496981;179496980 |
| N2B | 5482 | 16669;16670;16671 | chr2:178632255;178632254;178632253 | chr2:179496982;179496981;179496980 |
| Novex-1 | 5607 | 17044;17045;17046 | chr2:178632255;178632254;178632253 | chr2:179496982;179496981;179496980 |
| Novex-2 | 5674 | 17245;17246;17247 | chr2:178632255;178632254;178632253 | chr2:179496982;179496981;179496980 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/K | rs761539202  |
1.041 | 0.426 | D | 0.4 | 0.392 | 0.407082143382 | gnomAD-2.1.1 | 7.35E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.61E-05 | 0 |
| E/K | rs761539202 |
1.041 | 0.426 | D | 0.4 | 0.392 | 0.407082143382 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| E/K | rs761539202 |
1.041 | 0.426 | D | 0.4 | 0.392 | 0.407082143382 | gnomAD-4.0.0 | 1.30534E-05 | None | None | None | None | N | None | 1.33668E-05 | 0 | None | 3.40044E-05 | 0 | None | 0 | 0 | 1.44376E-05 | 0 | 3.21192E-05 |
| E/Q | rs761539202 |
0.854 | 0.405 | D | 0.381 | 0.361 | 0.457197642564 | gnomAD-2.1.1 | 4.15E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.18E-06 | 0 |
| E/Q | rs761539202 |
0.854 | 0.405 | D | 0.381 | 0.361 | 0.457197642564 | gnomAD-4.0.0 | 6.86468E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.01315E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.1096 | likely_benign | 0.1255 | benign | -0.266 | Destabilizing | None | N | 0.288 | neutral | D | 0.601001447 | None | None | N |
| E/C | 0.765 | likely_pathogenic | 0.7821 | pathogenic | 0.122 | Stabilizing | 0.824 | D | 0.407 | neutral | None | None | None | None | N |
| E/D | 0.1064 | likely_benign | 0.0924 | benign | -0.218 | Destabilizing | None | N | 0.165 | neutral | N | 0.420486225 | None | None | N |
| E/F | 0.5659 | likely_pathogenic | 0.5804 | pathogenic | -0.308 | Destabilizing | 0.555 | D | 0.381 | neutral | None | None | None | None | N |
| E/G | 0.1427 | likely_benign | 0.1443 | benign | -0.435 | Destabilizing | 0.062 | N | 0.399 | neutral | D | 0.601145245 | None | None | N |
| E/H | 0.3414 | ambiguous | 0.335 | benign | -0.089 | Destabilizing | 0.791 | D | 0.317 | neutral | None | None | None | None | N |
| E/I | 0.2399 | likely_benign | 0.2402 | benign | 0.132 | Stabilizing | 0.38 | N | 0.397 | neutral | None | None | None | None | N |
| E/K | 0.0942 | likely_benign | 0.0877 | benign | 0.418 | Stabilizing | 0.426 | N | 0.4 | neutral | D | 0.542900907 | None | None | N |
| E/L | 0.3218 | likely_benign | 0.3521 | ambiguous | 0.132 | Stabilizing | 0.081 | N | 0.397 | neutral | None | None | None | None | N |
| E/M | 0.3274 | likely_benign | 0.3461 | ambiguous | 0.249 | Stabilizing | 0.824 | D | 0.394 | neutral | None | None | None | None | N |
| E/N | 0.1823 | likely_benign | 0.1672 | benign | 0.243 | Stabilizing | 0.081 | N | 0.361 | neutral | None | None | None | None | N |
| E/P | 0.7946 | likely_pathogenic | 0.8175 | pathogenic | 0.019 | Stabilizing | 0.38 | N | 0.347 | neutral | None | None | None | None | N |
| E/Q | 0.1359 | likely_benign | 0.1347 | benign | 0.254 | Stabilizing | 0.405 | N | 0.381 | neutral | D | 0.546598364 | None | None | N |
| E/R | 0.1686 | likely_benign | 0.165 | benign | 0.544 | Stabilizing | 0.38 | N | 0.331 | neutral | None | None | None | None | N |
| E/S | 0.1495 | likely_benign | 0.1501 | benign | 0.066 | Stabilizing | 0.081 | N | 0.373 | neutral | None | None | None | None | N |
| E/T | 0.157 | likely_benign | 0.1598 | benign | 0.2 | Stabilizing | 0.081 | N | 0.389 | neutral | None | None | None | None | N |
| E/V | 0.1523 | likely_benign | 0.158 | benign | 0.019 | Stabilizing | 0.062 | N | 0.394 | neutral | D | 0.546598364 | None | None | N |
| E/W | 0.7956 | likely_pathogenic | 0.7881 | pathogenic | -0.221 | Destabilizing | 0.935 | D | 0.507 | neutral | None | None | None | None | N |
| E/Y | 0.4775 | ambiguous | 0.4706 | ambiguous | -0.076 | Destabilizing | 0.555 | D | 0.385 | 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.