Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28805 | 86638;86639;86640 | chr2:178559719;178559718;178559717 | chr2:179424446;179424445;179424444 |
| N2AB | 27164 | 81715;81716;81717 | chr2:178559719;178559718;178559717 | chr2:179424446;179424445;179424444 |
| N2A | 26237 | 78934;78935;78936 | chr2:178559719;178559718;178559717 | chr2:179424446;179424445;179424444 |
| N2B | 19740 | 59443;59444;59445 | chr2:178559719;178559718;178559717 | chr2:179424446;179424445;179424444 |
| Novex-1 | 19865 | 59818;59819;59820 | chr2:178559719;178559718;178559717 | chr2:179424446;179424445;179424444 |
| Novex-2 | 19932 | 60019;60020;60021 | chr2:178559719;178559718;178559717 | chr2:179424446;179424445;179424444 |
| 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/A | rs1028838136  |
-0.405 | 0.062 | N | 0.317 | 0.112 | 0.216624796971 | gnomAD-2.1.1 | 4.2E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.24E-06 | 0 |
| D/A | rs1028838136 |
-0.405 | 0.062 | N | 0.317 | 0.112 | 0.216624796971 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| D/A | rs1028838136 |
-0.405 | 0.062 | N | 0.317 | 0.112 | 0.216624796971 | gnomAD-4.0.0 | 5.20649E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.72545E-06 | 0 | 0 |
| D/G | rs1028838136 |
-0.842 | 0.062 | N | 0.269 | 0.088 | 0.143124449307 | gnomAD-2.1.1 | 6.38E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.29735E-04 | 0 |
| D/G | rs1028838136 |
-0.842 | 0.062 | N | 0.269 | 0.088 | 0.143124449307 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| D/G | rs1028838136 |
-0.842 | 0.062 | N | 0.269 | 0.088 | 0.143124449307 | gnomAD-4.0.0 | 1.97342E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.41189E-05 | 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 | 0.1325 | likely_benign | 0.1503 | benign | -0.14 | Destabilizing | 0.062 | N | 0.317 | neutral | N | 0.505098499 | None | None | N |
| D/C | 0.5306 | ambiguous | 0.5704 | pathogenic | -0.097 | Destabilizing | 0.935 | D | 0.464 | neutral | None | None | None | None | N |
| D/E | 0.1214 | likely_benign | 0.1189 | benign | -0.27 | Destabilizing | None | N | 0.211 | neutral | N | 0.417959517 | None | None | N |
| D/F | 0.5349 | ambiguous | 0.5648 | pathogenic | 0.008 | Stabilizing | 0.555 | D | 0.422 | neutral | None | None | None | None | N |
| D/G | 0.1454 | likely_benign | 0.1679 | benign | -0.321 | Destabilizing | 0.062 | N | 0.269 | neutral | N | 0.48021591 | None | None | N |
| D/H | 0.3028 | likely_benign | 0.3468 | ambiguous | 0.434 | Stabilizing | 0.78 | D | 0.297 | neutral | N | 0.460099887 | None | None | N |
| D/I | 0.3005 | likely_benign | 0.3303 | benign | 0.284 | Stabilizing | 0.235 | N | 0.424 | neutral | None | None | None | None | N |
| D/K | 0.3749 | ambiguous | 0.414 | ambiguous | 0.459 | Stabilizing | 0.081 | N | 0.256 | neutral | None | None | None | None | N |
| D/L | 0.3294 | likely_benign | 0.3606 | ambiguous | 0.284 | Stabilizing | 0.235 | N | 0.379 | neutral | None | None | None | None | N |
| D/M | 0.5126 | ambiguous | 0.5529 | ambiguous | 0.194 | Stabilizing | 0.824 | D | 0.431 | neutral | None | None | None | None | N |
| D/N | 0.1021 | likely_benign | 0.1125 | benign | -0.003 | Destabilizing | 0.117 | N | 0.329 | neutral | N | 0.47541031 | None | None | N |
| D/P | 0.4046 | ambiguous | 0.4283 | ambiguous | 0.165 | Stabilizing | 0.555 | D | 0.289 | neutral | None | None | None | None | N |
| D/Q | 0.3098 | likely_benign | 0.3434 | ambiguous | 0.05 | Stabilizing | 0.235 | N | 0.276 | neutral | None | None | None | None | N |
| D/R | 0.4285 | ambiguous | 0.4707 | ambiguous | 0.712 | Stabilizing | 0.001 | N | 0.289 | neutral | None | None | None | None | N |
| D/S | 0.1061 | likely_benign | 0.1176 | benign | -0.064 | Destabilizing | 0.002 | N | 0.218 | neutral | None | None | None | None | N |
| D/T | 0.1967 | likely_benign | 0.227 | benign | 0.089 | Stabilizing | 0.001 | N | 0.223 | neutral | None | None | None | None | N |
| D/V | 0.1875 | likely_benign | 0.2061 | benign | 0.165 | Stabilizing | 0.188 | N | 0.38 | neutral | N | 0.460606866 | None | None | N |
| D/W | 0.8591 | likely_pathogenic | 0.8834 | pathogenic | 0.145 | Stabilizing | 0.935 | D | 0.544 | neutral | None | None | None | None | N |
| D/Y | 0.2413 | likely_benign | 0.2707 | benign | 0.257 | Stabilizing | 0.484 | N | 0.423 | neutral | N | 0.483484061 | 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.