Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15690 | 47293;47294;47295 | chr2:178618390;178618389;178618388 | chr2:179483117;179483116;179483115 |
| N2AB | 14049 | 42370;42371;42372 | chr2:178618390;178618389;178618388 | chr2:179483117;179483116;179483115 |
| N2A | 13122 | 39589;39590;39591 | chr2:178618390;178618389;178618388 | chr2:179483117;179483116;179483115 |
| N2B | 6625 | 20098;20099;20100 | chr2:178618390;178618389;178618388 | chr2:179483117;179483116;179483115 |
| Novex-1 | 6750 | 20473;20474;20475 | chr2:178618390;178618389;178618388 | chr2:179483117;179483116;179483115 |
| Novex-2 | 6817 | 20674;20675;20676 | chr2:178618390;178618389;178618388 | chr2:179483117;179483116;179483115 |
| 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/L | None | None | 0.002 | N | 0.051 | 0.071 | 0.411133732114 | gnomAD-4.0.0 | 6.84722E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15972E-05 | 0 |
| I/M | rs1399689836  |
-0.357 | 0.934 | N | 0.392 | 0.115 | 0.509346181843 | 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 |
| I/M | rs1399689836 |
-0.357 | 0.934 | N | 0.392 | 0.115 | 0.509346181843 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/M | rs1399689836 |
-0.357 | 0.934 | N | 0.392 | 0.115 | 0.509346181843 | gnomAD-4.0.0 | 6.58241E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47284E-05 | 0 | 0 |
| I/V | None | None | 0.267 | N | 0.204 | 0.04 | 0.363356657567 | gnomAD-4.0.0 | 1.36945E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79985E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1935 | likely_benign | 0.2175 | benign | -0.818 | Destabilizing | 0.525 | D | 0.411 | neutral | None | None | None | None | I |
| I/C | 0.7336 | likely_pathogenic | 0.7073 | pathogenic | -0.768 | Destabilizing | 0.998 | D | 0.377 | neutral | None | None | None | None | I |
| I/D | 0.7272 | likely_pathogenic | 0.6515 | pathogenic | -0.308 | Destabilizing | 0.949 | D | 0.381 | neutral | None | None | None | None | I |
| I/E | 0.5792 | likely_pathogenic | 0.4807 | ambiguous | -0.391 | Destabilizing | 0.949 | D | 0.381 | neutral | None | None | None | None | I |
| I/F | 0.2114 | likely_benign | 0.2204 | benign | -0.727 | Destabilizing | 0.949 | D | 0.351 | neutral | None | None | None | None | I |
| I/G | 0.6072 | likely_pathogenic | 0.5914 | pathogenic | -0.995 | Destabilizing | 0.842 | D | 0.383 | neutral | None | None | None | None | I |
| I/H | 0.582 | likely_pathogenic | 0.5334 | ambiguous | -0.15 | Destabilizing | 0.998 | D | 0.34 | neutral | None | None | None | None | I |
| I/K | 0.4838 | ambiguous | 0.4315 | ambiguous | -0.515 | Destabilizing | 0.934 | D | 0.383 | neutral | N | 0.469766204 | None | None | I |
| I/L | 0.0987 | likely_benign | 0.091 | benign | -0.468 | Destabilizing | 0.002 | N | 0.051 | neutral | N | 0.389384786 | None | None | I |
| I/M | 0.0993 | likely_benign | 0.1045 | benign | -0.495 | Destabilizing | 0.934 | D | 0.392 | neutral | N | 0.477792751 | None | None | I |
| I/N | 0.326 | likely_benign | 0.2855 | benign | -0.365 | Destabilizing | 0.949 | D | 0.395 | neutral | None | None | None | None | I |
| I/P | 0.875 | likely_pathogenic | 0.8823 | pathogenic | -0.552 | Destabilizing | 0.974 | D | 0.407 | neutral | None | None | None | None | I |
| I/Q | 0.4764 | ambiguous | 0.4009 | ambiguous | -0.596 | Destabilizing | 0.974 | D | 0.385 | neutral | None | None | None | None | I |
| I/R | 0.3947 | ambiguous | 0.3706 | ambiguous | 0.106 | Stabilizing | 0.934 | D | 0.408 | neutral | N | 0.472368089 | None | None | I |
| I/S | 0.2121 | likely_benign | 0.2127 | benign | -0.843 | Destabilizing | 0.728 | D | 0.334 | neutral | None | None | None | None | I |
| I/T | 0.073 | likely_benign | 0.0819 | benign | -0.817 | Destabilizing | 0.022 | N | 0.119 | neutral | N | 0.348365058 | None | None | I |
| I/V | 0.0869 | likely_benign | 0.0893 | benign | -0.552 | Destabilizing | 0.267 | N | 0.204 | neutral | N | 0.469009987 | None | None | I |
| I/W | 0.7923 | likely_pathogenic | 0.7573 | pathogenic | -0.714 | Destabilizing | 0.998 | D | 0.391 | neutral | None | None | None | None | I |
| I/Y | 0.604 | likely_pathogenic | 0.5869 | pathogenic | -0.49 | Destabilizing | 0.991 | D | 0.4 | 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.