Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26983 | 81172;81173;81174 | chr2:178565185;178565184;178565183 | chr2:179429912;179429911;179429910 |
| N2AB | 25342 | 76249;76250;76251 | chr2:178565185;178565184;178565183 | chr2:179429912;179429911;179429910 |
| N2A | 24415 | 73468;73469;73470 | chr2:178565185;178565184;178565183 | chr2:179429912;179429911;179429910 |
| N2B | 17918 | 53977;53978;53979 | chr2:178565185;178565184;178565183 | chr2:179429912;179429911;179429910 |
| Novex-1 | 18043 | 54352;54353;54354 | chr2:178565185;178565184;178565183 | chr2:179429912;179429911;179429910 |
| Novex-2 | 18110 | 54553;54554;54555 | chr2:178565185;178565184;178565183 | chr2:179429912;179429911;179429910 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs775115560  |
-0.162 | 0.099 | N | 0.213 | 0.107 | 0.0716867268079 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| D/E | rs775115560 |
-0.162 | 0.099 | N | 0.213 | 0.107 | 0.0716867268079 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/E | rs775115560 |
-0.162 | 0.099 | N | 0.213 | 0.107 | 0.0716867268079 | gnomAD-4.0.0 | 6.57402E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.4705E-05 | 0 | 0 |
| D/N | None | None | 0.983 | N | 0.563 | 0.34 | 0.235664433957 | gnomAD-4.0.0 | 1.59197E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77639E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2945 | likely_benign | 0.3102 | benign | -0.625 | Destabilizing | 0.892 | D | 0.555 | neutral | N | 0.516017287 | None | None | I |
| D/C | 0.7283 | likely_pathogenic | 0.728 | pathogenic | -0.185 | Destabilizing | 0.999 | D | 0.72 | prob.delet. | None | None | None | None | I |
| D/E | 0.1836 | likely_benign | 0.184 | benign | -0.51 | Destabilizing | 0.099 | N | 0.213 | neutral | N | 0.452485883 | None | None | I |
| D/F | 0.7762 | likely_pathogenic | 0.7776 | pathogenic | -0.402 | Destabilizing | 0.975 | D | 0.705 | prob.neutral | None | None | None | None | I |
| D/G | 0.3408 | ambiguous | 0.3686 | ambiguous | -0.888 | Destabilizing | 0.944 | D | 0.583 | neutral | D | 0.523175332 | None | None | I |
| D/H | 0.4019 | ambiguous | 0.4149 | ambiguous | -0.457 | Destabilizing | 0.999 | D | 0.602 | neutral | N | 0.466520166 | None | None | I |
| D/I | 0.4824 | ambiguous | 0.4753 | ambiguous | 0.042 | Stabilizing | 0.95 | D | 0.687 | prob.neutral | None | None | None | None | I |
| D/K | 0.5324 | ambiguous | 0.5563 | ambiguous | -0.084 | Destabilizing | 0.916 | D | 0.586 | neutral | None | None | None | None | I |
| D/L | 0.4874 | ambiguous | 0.4808 | ambiguous | 0.042 | Stabilizing | 0.073 | N | 0.377 | neutral | None | None | None | None | I |
| D/M | 0.7021 | likely_pathogenic | 0.6859 | pathogenic | 0.349 | Stabilizing | 0.993 | D | 0.682 | prob.neutral | None | None | None | None | I |
| D/N | 0.1478 | likely_benign | 0.1405 | benign | -0.474 | Destabilizing | 0.983 | D | 0.563 | neutral | N | 0.506936444 | None | None | I |
| D/P | 0.9319 | likely_pathogenic | 0.9408 | pathogenic | -0.158 | Destabilizing | 0.996 | D | 0.649 | neutral | None | None | None | None | I |
| D/Q | 0.4371 | ambiguous | 0.4453 | ambiguous | -0.416 | Destabilizing | 0.975 | D | 0.568 | neutral | None | None | None | None | I |
| D/R | 0.5891 | likely_pathogenic | 0.622 | pathogenic | 0.11 | Stabilizing | 0.975 | D | 0.681 | prob.neutral | None | None | None | None | I |
| D/S | 0.1747 | likely_benign | 0.1755 | benign | -0.634 | Destabilizing | 0.916 | D | 0.567 | neutral | None | None | None | None | I |
| D/T | 0.2928 | likely_benign | 0.2958 | benign | -0.427 | Destabilizing | 0.975 | D | 0.572 | neutral | None | None | None | None | I |
| D/V | 0.3078 | likely_benign | 0.3176 | benign | -0.158 | Destabilizing | 0.935 | D | 0.576 | neutral | N | 0.463049593 | None | None | I |
| D/W | 0.9343 | likely_pathogenic | 0.9449 | pathogenic | -0.197 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | I |
| D/Y | 0.4248 | ambiguous | 0.4587 | ambiguous | -0.16 | Destabilizing | 0.983 | D | 0.698 | prob.neutral | N | 0.475167446 | 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.