Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4607 | 14044;14045;14046 | chr2:178739414;178739413;178739412 | chr2:179604141;179604140;179604139 |
| N2AB | 4290 | 13093;13094;13095 | chr2:178739414;178739413;178739412 | chr2:179604141;179604140;179604139 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 4244 | 12955;12956;12957 | chr2:178739414;178739413;178739412 | chr2:179604141;179604140;179604139 |
| Novex-1 | 4369 | 13330;13331;13332 | chr2:178739414;178739413;178739412 | chr2:179604141;179604140;179604139 |
| Novex-2 | 4436 | 13531;13532;13533 | chr2:178739414;178739413;178739412 | chr2:179604141;179604140;179604139 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/K | rs1391877719  |
None | 0.001 | N | 0.277 | 0.085 | None | gnomAD-4.0.0 | 1.59119E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85796E-06 | 0 | 0 |
| M/V | rs371275648 |
-1.154 | None | N | 0.077 | 0.139 | None | gnomAD-2.1.1 | 8.93E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.87832E-04 | 0 |
| M/V | rs371275648 |
-1.154 | None | N | 0.077 | 0.139 | None | gnomAD-3.1.2 | 5.91E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.02899E-04 | 0 | 0 |
| M/V | rs371275648 |
-1.154 | None | N | 0.077 | 0.139 | None | gnomAD-4.0.0 | 7.86978E-05 | None | None | None | None | N | None | 2.66923E-05 | 0 | None | 0 | 0 | None | 3.12432E-05 | 0 | 1.00862E-04 | 0 | 6.4041E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.1528 | likely_benign | 0.1564 | benign | -1.408 | Destabilizing | None | N | 0.158 | neutral | None | None | None | None | N |
| M/C | 0.3651 | ambiguous | 0.4556 | ambiguous | -0.581 | Destabilizing | 0.041 | N | 0.457 | neutral | None | None | None | None | N |
| M/D | 0.2669 | likely_benign | 0.2982 | benign | -0.367 | Destabilizing | None | N | 0.243 | neutral | None | None | None | None | N |
| M/E | 0.1329 | likely_benign | 0.1432 | benign | -0.392 | Destabilizing | 0.001 | N | 0.307 | neutral | None | None | None | None | N |
| M/F | 0.1612 | likely_benign | 0.1846 | benign | -0.736 | Destabilizing | 0.004 | N | 0.245 | neutral | None | None | None | None | N |
| M/G | 0.2479 | likely_benign | 0.2543 | benign | -1.642 | Destabilizing | None | N | 0.231 | neutral | None | None | None | None | N |
| M/H | 0.2343 | likely_benign | 0.2645 | benign | -0.701 | Destabilizing | 0.132 | N | 0.485 | neutral | None | None | None | None | N |
| M/I | 0.0958 | likely_benign | 0.1044 | benign | -0.838 | Destabilizing | None | N | 0.08 | neutral | N | 0.38553326 | None | None | N |
| M/K | 0.1291 | likely_benign | 0.115 | benign | -0.296 | Destabilizing | 0.001 | N | 0.277 | neutral | N | 0.358891447 | None | None | N |
| M/L | 0.1096 | likely_benign | 0.1097 | benign | -0.838 | Destabilizing | None | N | 0.075 | neutral | N | 0.375584568 | None | None | N |
| M/N | 0.1617 | likely_benign | 0.1884 | benign | -0.033 | Destabilizing | 0.002 | N | 0.28 | neutral | None | None | None | None | N |
| M/P | 0.7034 | likely_pathogenic | 0.7201 | pathogenic | -1.002 | Destabilizing | 0.004 | N | 0.301 | neutral | None | None | None | None | N |
| M/Q | 0.1268 | likely_benign | 0.1225 | benign | -0.206 | Destabilizing | 0.009 | N | 0.277 | neutral | None | None | None | None | N |
| M/R | 0.1087 | likely_benign | 0.1029 | benign | 0.302 | Stabilizing | 0.007 | N | 0.34 | neutral | N | 0.384886102 | None | None | N |
| M/S | 0.1482 | likely_benign | 0.1563 | benign | -0.539 | Destabilizing | 0.001 | N | 0.286 | neutral | None | None | None | None | N |
| M/T | 0.1166 | likely_benign | 0.1061 | benign | -0.467 | Destabilizing | None | N | 0.16 | neutral | N | 0.341687011 | None | None | N |
| M/V | 0.0498 | likely_benign | 0.0439 | benign | -1.002 | Destabilizing | None | N | 0.077 | neutral | N | 0.284743331 | None | None | N |
| M/W | 0.4464 | ambiguous | 0.4772 | ambiguous | -0.629 | Destabilizing | 0.316 | N | 0.363 | neutral | None | None | None | None | N |
| M/Y | 0.324 | likely_benign | 0.3727 | ambiguous | -0.639 | Destabilizing | 0.018 | N | 0.351 | 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.