Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25146 | 75661;75662;75663 | chr2:178570696;178570695;178570694 | chr2:179435423;179435422;179435421 |
| N2AB | 23505 | 70738;70739;70740 | chr2:178570696;178570695;178570694 | chr2:179435423;179435422;179435421 |
| N2A | 22578 | 67957;67958;67959 | chr2:178570696;178570695;178570694 | chr2:179435423;179435422;179435421 |
| N2B | 16081 | 48466;48467;48468 | chr2:178570696;178570695;178570694 | chr2:179435423;179435422;179435421 |
| Novex-1 | 16206 | 48841;48842;48843 | chr2:178570696;178570695;178570694 | chr2:179435423;179435422;179435421 |
| Novex-2 | 16273 | 49042;49043;49044 | chr2:178570696;178570695;178570694 | chr2:179435423;179435422;179435421 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/K | None | None | 0.055 | N | 0.577 | 0.184 | 0.32980341726 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/M | rs957042580  |
None | 0.093 | N | 0.492 | 0.017 | 0.186928172975 | gnomAD-4.0.0 | 6.84293E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99577E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1876 | likely_benign | 0.1939 | benign | -2.226 | Highly Destabilizing | None | N | 0.253 | neutral | None | None | None | None | N |
| I/C | 0.3274 | likely_benign | 0.3421 | ambiguous | -1.48 | Destabilizing | 0.001 | N | 0.37 | neutral | None | None | None | None | N |
| I/D | 0.3871 | ambiguous | 0.4125 | ambiguous | -1.938 | Destabilizing | 0.072 | N | 0.604 | neutral | None | None | None | None | N |
| I/E | 0.229 | likely_benign | 0.2517 | benign | -1.765 | Destabilizing | 0.072 | N | 0.569 | neutral | None | None | None | None | N |
| I/F | 0.08 | likely_benign | 0.0759 | benign | -1.249 | Destabilizing | None | N | 0.315 | neutral | None | None | None | None | N |
| I/G | 0.3246 | likely_benign | 0.3492 | ambiguous | -2.722 | Highly Destabilizing | 0.038 | N | 0.534 | neutral | None | None | None | None | N |
| I/H | 0.1974 | likely_benign | 0.2102 | benign | -2.037 | Highly Destabilizing | 0.628 | D | 0.582 | neutral | None | None | None | None | N |
| I/K | 0.1497 | likely_benign | 0.1678 | benign | -1.595 | Destabilizing | 0.055 | N | 0.577 | neutral | N | 0.411609548 | None | None | N |
| I/L | 0.0577 | likely_benign | 0.0623 | benign | -0.83 | Destabilizing | None | N | 0.151 | neutral | N | 0.345421841 | None | None | N |
| I/M | 0.0558 | likely_benign | 0.0563 | benign | -0.781 | Destabilizing | 0.093 | N | 0.492 | neutral | N | 0.428656513 | None | None | N |
| I/N | 0.1137 | likely_benign | 0.1232 | benign | -1.737 | Destabilizing | 0.072 | N | 0.636 | neutral | None | None | None | None | N |
| I/P | 0.9189 | likely_pathogenic | 0.9276 | pathogenic | -1.272 | Destabilizing | 0.356 | N | 0.631 | neutral | None | None | None | None | N |
| I/Q | 0.1455 | likely_benign | 0.1612 | benign | -1.671 | Destabilizing | 0.214 | N | 0.62 | neutral | None | None | None | None | N |
| I/R | 0.1112 | likely_benign | 0.1277 | benign | -1.259 | Destabilizing | 0.171 | N | 0.633 | neutral | N | 0.419324954 | None | None | N |
| I/S | 0.1189 | likely_benign | 0.1261 | benign | -2.494 | Highly Destabilizing | 0.001 | N | 0.359 | neutral | None | None | None | None | N |
| I/T | 0.1191 | likely_benign | 0.1178 | benign | -2.184 | Highly Destabilizing | None | N | 0.26 | neutral | N | 0.414591138 | None | None | N |
| I/V | 0.0695 | likely_benign | 0.0669 | benign | -1.272 | Destabilizing | None | N | 0.194 | neutral | N | 0.452552093 | None | None | N |
| I/W | 0.4001 | ambiguous | 0.4122 | ambiguous | -1.533 | Destabilizing | 0.864 | D | 0.593 | neutral | None | None | None | None | N |
| I/Y | 0.208 | likely_benign | 0.2272 | benign | -1.256 | Destabilizing | 0.038 | N | 0.585 | 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.