Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4922 | 14989;14990;14991 | chr2:178735682;178735681;178735680 | chr2:179600409;179600408;179600407 |
| N2AB | 4605 | 14038;14039;14040 | chr2:178735682;178735681;178735680 | chr2:179600409;179600408;179600407 |
| N2A | 3678 | 11257;11258;11259 | chr2:178735682;178735681;178735680 | chr2:179600409;179600408;179600407 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs184740744  |
-0.041 | None | D | 0.163 | 0.119 | None | gnomAD-2.1.1 | 5.31717E-03 | None | None | None | None | N | None | 3.72024E-04 | 4.10815E-02 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 2.34E-05 | 3.23944E-03 |
| S/N | rs184740744 |
-0.041 | None | D | 0.163 | 0.119 | None | gnomAD-3.1.2 | 1.89924E-03 | None | None | None | None | N | None | 4.58472E-04 | 1.74289E-02 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07297E-04 | 1.43403E-03 |
| S/N | rs184740744 |
-0.041 | None | D | 0.163 | 0.119 | None | 1000 genomes | 3.99361E-03 | None | None | None | None | N | None | 0 | 2.74E-02 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| S/N | rs184740744 |
-0.041 | None | D | 0.163 | 0.119 | None | gnomAD-4.0.0 | 1.27401E-03 | None | None | None | None | N | None | 4.7977E-04 | 3.25344E-02 | None | 0 | 0 | None | 0 | 0 | 3.39035E-06 | 7.68623E-05 | 9.1238E-04 |
| S/R | rs2081320760 |
None | 0.055 | N | 0.516 | 0.156 | 0.137902524267 | gnomAD-4.0.0 | 1.59138E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85812E-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 | 0.1007 | likely_benign | 0.1097 | benign | -1.002 | Destabilizing | 0.007 | N | 0.363 | neutral | None | None | None | None | N |
| S/C | 0.0858 | likely_benign | 0.0851 | benign | -0.517 | Destabilizing | 0.56 | D | 0.551 | neutral | D | 0.579120502 | None | None | N |
| S/D | 0.1622 | likely_benign | 0.2006 | benign | -0.434 | Destabilizing | 0.016 | N | 0.413 | neutral | None | None | None | None | N |
| S/E | 0.2161 | likely_benign | 0.2547 | benign | -0.285 | Destabilizing | 0.016 | N | 0.407 | neutral | None | None | None | None | N |
| S/F | 0.1661 | likely_benign | 0.1841 | benign | -1.012 | Destabilizing | 0.214 | N | 0.602 | neutral | None | None | None | None | N |
| S/G | 0.0962 | likely_benign | 0.1016 | benign | -1.36 | Destabilizing | 0.012 | N | 0.417 | neutral | D | 0.600293922 | None | None | N |
| S/H | 0.1146 | likely_benign | 0.1231 | benign | -1.609 | Destabilizing | 0.214 | N | 0.561 | neutral | None | None | None | None | N |
| S/I | 0.0796 | likely_benign | 0.0825 | benign | -0.101 | Destabilizing | None | N | 0.321 | neutral | N | 0.460229195 | None | None | N |
| S/K | 0.2096 | likely_benign | 0.2244 | benign | 0.052 | Stabilizing | 0.016 | N | 0.411 | neutral | None | None | None | None | N |
| S/L | 0.0938 | likely_benign | 0.0976 | benign | -0.101 | Destabilizing | 0.002 | N | 0.439 | neutral | None | None | None | None | N |
| S/M | 0.1165 | likely_benign | 0.1202 | benign | -0.044 | Destabilizing | 0.003 | N | 0.369 | neutral | None | None | None | None | N |
| S/N | 0.0567 | likely_benign | 0.0577 | benign | -0.392 | Destabilizing | None | N | 0.163 | neutral | D | 0.52885488 | None | None | N |
| S/P | 0.8543 | likely_pathogenic | 0.8912 | pathogenic | -0.368 | Destabilizing | 0.136 | N | 0.55 | neutral | None | None | None | None | N |
| S/Q | 0.184 | likely_benign | 0.199 | benign | -0.285 | Destabilizing | 0.072 | N | 0.498 | neutral | None | None | None | None | N |
| S/R | 0.1966 | likely_benign | 0.2152 | benign | -0.254 | Destabilizing | 0.055 | N | 0.516 | neutral | N | 0.435031367 | None | None | N |
| S/T | 0.0744 | likely_benign | 0.0786 | benign | -0.31 | Destabilizing | None | N | 0.163 | neutral | N | 0.435821597 | None | None | N |
| S/V | 0.1104 | likely_benign | 0.1187 | benign | -0.368 | Destabilizing | 0.002 | N | 0.452 | neutral | None | None | None | None | N |
| S/W | 0.2335 | likely_benign | 0.2515 | benign | -1.035 | Destabilizing | 0.864 | D | 0.604 | neutral | None | None | None | None | N |
| S/Y | 0.0953 | likely_benign | 0.104 | benign | -0.662 | Destabilizing | 0.356 | N | 0.601 | 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.