Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18012 | 54259;54260;54261 | chr2:178605143;178605142;178605141 | chr2:179469870;179469869;179469868 |
| N2AB | 16371 | 49336;49337;49338 | chr2:178605143;178605142;178605141 | chr2:179469870;179469869;179469868 |
| N2A | 15444 | 46555;46556;46557 | chr2:178605143;178605142;178605141 | chr2:179469870;179469869;179469868 |
| N2B | 8947 | 27064;27065;27066 | chr2:178605143;178605142;178605141 | chr2:179469870;179469869;179469868 |
| Novex-1 | 9072 | 27439;27440;27441 | chr2:178605143;178605142;178605141 | chr2:179469870;179469869;179469868 |
| Novex-2 | 9139 | 27640;27641;27642 | chr2:178605143;178605142;178605141 | chr2:179469870;179469869;179469868 |
| 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 | rs765319965  |
0.19 | None | N | 0.141 | 0.114 | 0.0482279557977 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/E | rs765319965 |
0.19 | None | N | 0.141 | 0.114 | 0.0482279557977 | gnomAD-4.0.0 | 3.42315E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69959E-06 | 1.16001E-05 | 1.65804E-05 |
| D/N | None | None | None | N | 0.172 | 0.112 | 0.216624796971 | gnomAD-4.0.0 | 1.59367E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86236E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.0613 | likely_benign | 0.0758 | benign | 0.086 | Stabilizing | 0.027 | N | 0.259 | neutral | N | 0.46336652 | None | None | N |
| D/C | 0.4115 | ambiguous | 0.4449 | ambiguous | 0.046 | Stabilizing | 0.935 | D | 0.257 | neutral | None | None | None | None | N |
| D/E | 0.0685 | likely_benign | 0.0801 | benign | -0.212 | Destabilizing | None | N | 0.141 | neutral | N | 0.409897394 | None | None | N |
| D/F | 0.3799 | ambiguous | 0.4359 | ambiguous | -0.088 | Destabilizing | 0.791 | D | 0.249 | neutral | None | None | None | None | N |
| D/G | 0.0915 | likely_benign | 0.099 | benign | -0.018 | Destabilizing | 0.027 | N | 0.307 | neutral | N | 0.433446257 | None | None | N |
| D/H | 0.1681 | likely_benign | 0.1693 | benign | 0.428 | Stabilizing | 0.484 | N | 0.272 | neutral | N | 0.471236641 | None | None | N |
| D/I | 0.1605 | likely_benign | 0.1959 | benign | 0.289 | Stabilizing | 0.555 | D | 0.278 | neutral | None | None | None | None | N |
| D/K | 0.1195 | likely_benign | 0.1365 | benign | 0.515 | Stabilizing | 0.081 | N | 0.303 | neutral | None | None | None | None | N |
| D/L | 0.1622 | likely_benign | 0.2031 | benign | 0.289 | Stabilizing | 0.149 | N | 0.324 | neutral | None | None | None | None | N |
| D/M | 0.2672 | likely_benign | 0.318 | benign | 0.16 | Stabilizing | 0.935 | D | 0.246 | neutral | None | None | None | None | N |
| D/N | 0.0769 | likely_benign | 0.0756 | benign | 0.394 | Stabilizing | None | N | 0.172 | neutral | N | 0.487070099 | None | None | N |
| D/P | 0.1749 | likely_benign | 0.2208 | benign | 0.24 | Stabilizing | 0.001 | N | 0.213 | neutral | None | None | None | None | N |
| D/Q | 0.137 | likely_benign | 0.1569 | benign | 0.378 | Stabilizing | 0.081 | N | 0.277 | neutral | None | None | None | None | N |
| D/R | 0.1871 | likely_benign | 0.2027 | benign | 0.671 | Stabilizing | 0.235 | N | 0.297 | neutral | None | None | None | None | N |
| D/S | 0.0725 | likely_benign | 0.0759 | benign | 0.274 | Stabilizing | 0.002 | N | 0.168 | neutral | None | None | None | None | N |
| D/T | 0.0934 | likely_benign | 0.1132 | benign | 0.355 | Stabilizing | 0.081 | N | 0.313 | neutral | None | None | None | None | N |
| D/V | 0.1 | likely_benign | 0.1209 | benign | 0.24 | Stabilizing | 0.117 | N | 0.325 | neutral | N | 0.488283607 | None | None | N |
| D/W | 0.703 | likely_pathogenic | 0.7412 | pathogenic | -0.081 | Destabilizing | 0.935 | D | 0.381 | neutral | None | None | None | None | N |
| D/Y | 0.1818 | likely_benign | 0.1888 | benign | 0.133 | Stabilizing | 0.741 | D | 0.249 | neutral | N | 0.470428565 | 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.