Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25065 | 75418;75419;75420 | chr2:178570939;178570938;178570937 | chr2:179435666;179435665;179435664 |
| N2AB | 23424 | 70495;70496;70497 | chr2:178570939;178570938;178570937 | chr2:179435666;179435665;179435664 |
| N2A | 22497 | 67714;67715;67716 | chr2:178570939;178570938;178570937 | chr2:179435666;179435665;179435664 |
| N2B | 16000 | 48223;48224;48225 | chr2:178570939;178570938;178570937 | chr2:179435666;179435665;179435664 |
| Novex-1 | 16125 | 48598;48599;48600 | chr2:178570939;178570938;178570937 | chr2:179435666;179435665;179435664 |
| Novex-2 | 16192 | 48799;48800;48801 | chr2:178570939;178570938;178570937 | chr2:179435666;179435665;179435664 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/N | rs1318351282  |
-0.356 | 0.006 | N | 0.225 | 0.093 | 0.168933306366 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| H/P | rs182161195 |
0.215 | 0.028 | N | 0.35 | 0.254 | 0.366848117066 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14784E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| H/R | rs182161195 |
-0.626 | 0.003 | N | 0.238 | 0.143 | None | gnomAD-2.1.1 | 2.64306E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 3.6942E-03 | None | 0 | None | 0 | 7.82E-06 | 1.40568E-04 |
| H/R | rs182161195 |
-0.626 | 0.003 | N | 0.238 | 0.143 | None | gnomAD-3.1.2 | 1.18371E-04 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 3.48972E-03 | None | 0 | 0 | 0 | 0 | 0 |
| H/R | rs182161195 |
-0.626 | 0.003 | N | 0.238 | 0.143 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 3E-03 | 0 | None | None | None | 0 | None |
| H/R | rs182161195 |
-0.626 | 0.003 | N | 0.238 | 0.143 | None | gnomAD-4.0.0 | 2.07622E-04 | None | None | None | None | I | None | 0 | 1.66639E-05 | None | 0 | 7.31588E-03 | None | 0 | 0 | 3.39106E-06 | 0 | 3.20215E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.1426 | likely_benign | 0.1439 | benign | -0.707 | Destabilizing | 0.002 | N | 0.337 | neutral | None | None | None | None | I |
| H/C | 0.1097 | likely_benign | 0.1085 | benign | 0.114 | Stabilizing | 0.497 | N | 0.487 | neutral | None | None | None | None | I |
| H/D | 0.1652 | likely_benign | 0.1502 | benign | -0.797 | Destabilizing | 0.001 | N | 0.261 | neutral | N | 0.471938436 | None | None | I |
| H/E | 0.1287 | likely_benign | 0.131 | benign | -0.675 | Destabilizing | None | N | 0.097 | neutral | None | None | None | None | I |
| H/F | 0.2227 | likely_benign | 0.2296 | benign | 0.746 | Stabilizing | 0.22 | N | 0.435 | neutral | None | None | None | None | I |
| H/G | 0.2393 | likely_benign | 0.2296 | benign | -1.098 | Destabilizing | 0.008 | N | 0.367 | neutral | None | None | None | None | I |
| H/I | 0.1646 | likely_benign | 0.1629 | benign | 0.387 | Stabilizing | 0.085 | N | 0.497 | neutral | None | None | None | None | I |
| H/K | 0.128 | likely_benign | 0.131 | benign | -0.469 | Destabilizing | None | N | 0.185 | neutral | None | None | None | None | I |
| H/L | 0.0888 | likely_benign | 0.0848 | benign | 0.387 | Stabilizing | 0.006 | N | 0.371 | neutral | N | 0.47786433 | None | None | I |
| H/M | 0.2496 | likely_benign | 0.2524 | benign | 0.166 | Stabilizing | 0.245 | N | 0.579 | neutral | None | None | None | None | I |
| H/N | 0.0781 | likely_benign | 0.0727 | benign | -0.758 | Destabilizing | 0.006 | N | 0.225 | neutral | N | 0.435785634 | None | None | I |
| H/P | 0.6906 | likely_pathogenic | 0.6382 | pathogenic | 0.042 | Stabilizing | 0.028 | N | 0.35 | neutral | N | 0.466916618 | None | None | I |
| H/Q | 0.0786 | likely_benign | 0.0809 | benign | -0.479 | Destabilizing | None | N | 0.091 | neutral | N | 0.386050247 | None | None | I |
| H/R | 0.0697 | likely_benign | 0.0702 | benign | -1.046 | Destabilizing | 0.003 | N | 0.238 | neutral | N | 0.432051896 | None | None | I |
| H/S | 0.1115 | likely_benign | 0.1106 | benign | -0.685 | Destabilizing | 0.002 | N | 0.315 | neutral | None | None | None | None | I |
| H/T | 0.1031 | likely_benign | 0.1047 | benign | -0.452 | Destabilizing | 0.008 | N | 0.353 | neutral | None | None | None | None | I |
| H/V | 0.1196 | likely_benign | 0.1211 | benign | 0.042 | Stabilizing | 0.008 | N | 0.359 | neutral | None | None | None | None | I |
| H/W | 0.3341 | likely_benign | 0.3229 | benign | 1.085 | Stabilizing | 0.497 | N | 0.486 | neutral | None | None | None | None | I |
| H/Y | 0.0879 | likely_benign | 0.0856 | benign | 1.089 | Stabilizing | 0.028 | N | 0.325 | neutral | N | 0.456046263 | 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.