Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26931 | 81016;81017;81018 | chr2:178565341;178565340;178565339 | chr2:179430068;179430067;179430066 |
| N2AB | 25290 | 76093;76094;76095 | chr2:178565341;178565340;178565339 | chr2:179430068;179430067;179430066 |
| N2A | 24363 | 73312;73313;73314 | chr2:178565341;178565340;178565339 | chr2:179430068;179430067;179430066 |
| N2B | 17866 | 53821;53822;53823 | chr2:178565341;178565340;178565339 | chr2:179430068;179430067;179430066 |
| Novex-1 | 17991 | 54196;54197;54198 | chr2:178565341;178565340;178565339 | chr2:179430068;179430067;179430066 |
| Novex-2 | 18058 | 54397;54398;54399 | chr2:178565341;178565340;178565339 | chr2:179430068;179430067;179430066 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs1397026912  |
-0.308 | 0.958 | N | 0.366 | 0.333 | 0.29132392195 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| T/A | rs1397026912 |
-0.308 | 0.958 | N | 0.366 | 0.333 | 0.29132392195 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/A | rs1397026912 |
-0.308 | 0.958 | N | 0.366 | 0.333 | 0.29132392195 | gnomAD-4.0.0 | 8.05682E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.01721E-05 | 1.0982E-05 | 0 |
| T/I | None | None | 0.976 | N | 0.533 | 0.54 | 0.589131389434 | gnomAD-4.0.0 | 6.84272E-06 | None | None | None | None | N | None | 2.98918E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.09588E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1596 | likely_benign | 0.1364 | benign | -0.478 | Destabilizing | 0.958 | D | 0.366 | neutral | N | 0.485403295 | None | None | N |
| T/C | 0.6204 | likely_pathogenic | 0.5721 | pathogenic | -0.133 | Destabilizing | 1.0 | D | 0.615 | neutral | None | None | None | None | N |
| T/D | 0.3501 | ambiguous | 0.3101 | benign | -0.075 | Destabilizing | 0.998 | D | 0.598 | neutral | None | None | None | None | N |
| T/E | 0.4603 | ambiguous | 0.4067 | ambiguous | -0.158 | Destabilizing | 0.995 | D | 0.561 | neutral | None | None | None | None | N |
| T/F | 0.4085 | ambiguous | 0.348 | ambiguous | -1.0 | Destabilizing | 0.991 | D | 0.691 | prob.neutral | None | None | None | None | N |
| T/G | 0.2568 | likely_benign | 0.2161 | benign | -0.606 | Destabilizing | 0.995 | D | 0.576 | neutral | None | None | None | None | N |
| T/H | 0.3943 | ambiguous | 0.3422 | ambiguous | -1.022 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| T/I | 0.4238 | ambiguous | 0.3528 | ambiguous | -0.256 | Destabilizing | 0.976 | D | 0.533 | neutral | N | 0.498191632 | None | None | N |
| T/K | 0.2598 | likely_benign | 0.2464 | benign | -0.355 | Destabilizing | 0.988 | D | 0.551 | neutral | N | 0.519935531 | None | None | N |
| T/L | 0.179 | likely_benign | 0.1593 | benign | -0.256 | Destabilizing | 0.839 | D | 0.415 | neutral | None | None | None | None | N |
| T/M | 0.1226 | likely_benign | 0.1124 | benign | 0.196 | Stabilizing | 0.862 | D | 0.336 | neutral | None | None | None | None | N |
| T/N | 0.1029 | likely_benign | 0.098 | benign | -0.089 | Destabilizing | 0.995 | D | 0.561 | neutral | None | None | None | None | N |
| T/P | 0.584 | likely_pathogenic | 0.5555 | ambiguous | -0.303 | Destabilizing | 0.998 | D | 0.583 | neutral | N | 0.507737512 | None | None | N |
| T/Q | 0.3761 | ambiguous | 0.3369 | benign | -0.419 | Destabilizing | 0.995 | D | 0.609 | neutral | None | None | None | None | N |
| T/R | 0.2712 | likely_benign | 0.2478 | benign | -0.053 | Destabilizing | 0.994 | D | 0.584 | neutral | D | 0.53479034 | None | None | N |
| T/S | 0.1172 | likely_benign | 0.1013 | benign | -0.298 | Destabilizing | 0.958 | D | 0.366 | neutral | N | 0.451942457 | None | None | N |
| T/V | 0.3309 | likely_benign | 0.2745 | benign | -0.303 | Destabilizing | 0.938 | D | 0.371 | neutral | None | None | None | None | N |
| T/W | 0.7637 | likely_pathogenic | 0.7286 | pathogenic | -0.961 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| T/Y | 0.4372 | ambiguous | 0.3961 | ambiguous | -0.687 | Destabilizing | 0.995 | D | 0.694 | prob.neutral | None | None | 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.