Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9314 | 28165;28166;28167 | chr2:178711296;178711295;178711294 | chr2:179576023;179576022;179576021 |
| N2AB | 8997 | 27214;27215;27216 | chr2:178711296;178711295;178711294 | chr2:179576023;179576022;179576021 |
| N2A | 8070 | 24433;24434;24435 | chr2:178711296;178711295;178711294 | chr2:179576023;179576022;179576021 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs727505348  |
-0.917 | 0.334 | N | 0.305 | 0.151 | 0.324986149311 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| V/A | rs727505348 |
-0.917 | 0.334 | N | 0.305 | 0.151 | 0.324986149311 | gnomAD-4.0.0 | 8.89693E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69899E-06 | 1.16036E-04 | 0 |
| V/D | rs727505348 |
-0.477 | 0.379 | N | 0.357 | 0.199 | 0.591083742983 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| V/D | rs727505348 |
-0.477 | 0.379 | N | 0.357 | 0.199 | 0.591083742983 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07297E-04 | 0 |
| V/D | rs727505348 |
-0.477 | 0.379 | N | 0.357 | 0.199 | 0.591083742983 | gnomAD-4.0.0 | 4.33875E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.59312E-05 | 1.60108E-05 |
| V/I | None | None | 0.004 | N | 0.231 | 0.097 | 0.124217242631 | gnomAD-4.0.0 | 1.59238E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86056E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1062 | likely_benign | 0.1257 | benign | -0.708 | Destabilizing | 0.334 | N | 0.305 | neutral | N | 0.49033969 | None | None | I |
| V/C | 0.8648 | likely_pathogenic | 0.8482 | pathogenic | -0.661 | Destabilizing | 0.992 | D | 0.297 | neutral | None | None | None | None | I |
| V/D | 0.3924 | ambiguous | 0.4597 | ambiguous | -0.117 | Destabilizing | 0.379 | N | 0.357 | neutral | N | 0.499500678 | None | None | I |
| V/E | 0.2082 | likely_benign | 0.2506 | benign | -0.203 | Destabilizing | 0.009 | N | 0.146 | neutral | None | None | None | None | I |
| V/F | 0.21 | likely_benign | 0.2245 | benign | -0.755 | Destabilizing | 0.81 | D | 0.266 | neutral | N | 0.46834232 | None | None | I |
| V/G | 0.274 | likely_benign | 0.3277 | benign | -0.896 | Destabilizing | 0.004 | N | 0.227 | neutral | N | 0.482585462 | None | None | I |
| V/H | 0.6432 | likely_pathogenic | 0.65 | pathogenic | -0.432 | Destabilizing | 0.992 | D | 0.354 | neutral | None | None | None | None | I |
| V/I | 0.0749 | likely_benign | 0.0723 | benign | -0.349 | Destabilizing | 0.004 | N | 0.231 | neutral | N | 0.463443877 | None | None | I |
| V/K | 0.3728 | ambiguous | 0.3985 | ambiguous | -0.518 | Destabilizing | 0.617 | D | 0.379 | neutral | None | None | None | None | I |
| V/L | 0.1799 | likely_benign | 0.189 | benign | -0.349 | Destabilizing | 0.08 | N | 0.34 | neutral | N | 0.440663018 | None | None | I |
| V/M | 0.141 | likely_benign | 0.1475 | benign | -0.324 | Destabilizing | 0.85 | D | 0.281 | neutral | None | None | None | None | I |
| V/N | 0.3326 | likely_benign | 0.3365 | benign | -0.252 | Destabilizing | 0.92 | D | 0.391 | neutral | None | None | None | None | I |
| V/P | 0.4152 | ambiguous | 0.4801 | ambiguous | -0.432 | Destabilizing | 0.972 | D | 0.367 | neutral | None | None | None | None | I |
| V/Q | 0.3306 | likely_benign | 0.3602 | ambiguous | -0.468 | Destabilizing | 0.85 | D | 0.36 | neutral | None | None | None | None | I |
| V/R | 0.3058 | likely_benign | 0.3203 | benign | -0.034 | Destabilizing | 0.85 | D | 0.4 | neutral | None | None | None | None | I |
| V/S | 0.1852 | likely_benign | 0.206 | benign | -0.728 | Destabilizing | 0.617 | D | 0.339 | neutral | None | None | None | None | I |
| V/T | 0.1287 | likely_benign | 0.1338 | benign | -0.705 | Destabilizing | 0.617 | D | 0.234 | neutral | None | None | None | None | I |
| V/W | 0.8137 | likely_pathogenic | 0.8283 | pathogenic | -0.84 | Destabilizing | 0.992 | D | 0.471 | neutral | None | None | None | None | I |
| V/Y | 0.6135 | likely_pathogenic | 0.6234 | pathogenic | -0.537 | Destabilizing | 0.92 | D | 0.267 | neutral | None | None | None | None | I |
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.