Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 50 | 373;374;375 | chr2:178802285;178802284;178802283 | chr2:179667012;179667011;179667010 |
| N2AB | 50 | 373;374;375 | chr2:178802285;178802284;178802283 | chr2:179667012;179667011;179667010 |
| N2A | 50 | 373;374;375 | chr2:178802285;178802284;178802283 | chr2:179667012;179667011;179667010 |
| N2B | 50 | 373;374;375 | chr2:178802285;178802284;178802283 | chr2:179667012;179667011;179667010 |
| Novex-1 | 50 | 373;374;375 | chr2:178802285;178802284;178802283 | chr2:179667012;179667011;179667010 |
| Novex-2 | 50 | 373;374;375 | chr2:178802285;178802284;178802283 | chr2:179667012;179667011;179667010 |
| Novex-3 | 50 | 373;374;375 | chr2:178802285;178802284;178802283 | chr2:179667012;179667011;179667010 |
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/P | rs1217255349  |
-0.272 | 0.523 | N | 0.295 | 0.133 | 0.299086750705 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | 0.057(TCAP) | N | None | 1.15207E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/P | rs1217255349 |
-0.272 | 0.523 | N | 0.295 | 0.133 | 0.299086750705 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | 0.057(TCAP) | N | None | 4.84E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/P | rs1217255349 |
-0.272 | 0.523 | N | 0.295 | 0.133 | 0.299086750705 | gnomAD-4.0.0 | 1.31744E-05 | None | None | None | 0.057(TCAP) | N | None | 4.84097E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | None | None | None | N | 0.26 | 0.07 | 0.124217242631 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | -0.183(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 | 0.0839 | likely_benign | 0.0971 | benign | -0.581 | Destabilizing | None | N | 0.199 | neutral | N | 0.454013095 | None | 0.117(TCAP) | N |
| T/C | 0.7948 | likely_pathogenic | 0.8778 | pathogenic | -0.326 | Destabilizing | 0.95 | D | 0.322 | neutral | None | None | None | 0.02(TCAP) | N |
| T/D | 0.3758 | ambiguous | 0.5134 | ambiguous | 0.46 | Stabilizing | 0.17 | N | 0.326 | neutral | None | None | None | 0.001(TCAP) | N |
| T/E | 0.3089 | likely_benign | 0.4293 | ambiguous | 0.41 | Stabilizing | 0.254 | N | 0.344 | neutral | None | None | None | -0.089(TCAP) | N |
| T/F | 0.3675 | ambiguous | 0.4701 | ambiguous | -1.046 | Destabilizing | 0.948 | D | 0.362 | neutral | None | None | None | 0.07(TCAP) | N |
| T/G | 0.2694 | likely_benign | 0.333 | benign | -0.739 | Destabilizing | 0.261 | N | 0.359 | neutral | None | None | None | 0.133(TCAP) | N |
| T/H | 0.3486 | ambiguous | 0.4621 | ambiguous | -1.123 | Destabilizing | 0.962 | D | 0.369 | neutral | None | None | None | 0.712(TCAP) | N |
| T/I | 0.2098 | likely_benign | 0.286 | benign | -0.277 | Destabilizing | 0.716 | D | 0.289 | neutral | N | 0.5011093 | None | 0.014(TCAP) | N |
| T/K | 0.2673 | likely_benign | 0.374 | ambiguous | -0.305 | Destabilizing | 0.323 | N | 0.343 | neutral | None | None | None | -0.152(TCAP) | N |
| T/L | 0.1286 | likely_benign | 0.1566 | benign | -0.277 | Destabilizing | 0.488 | N | 0.327 | neutral | None | None | None | 0.014(TCAP) | N |
| T/M | 0.1258 | likely_benign | 0.1464 | benign | -0.038 | Destabilizing | 0.987 | D | 0.323 | neutral | None | None | None | 0.261(TCAP) | N |
| T/N | 0.1425 | likely_benign | 0.185 | benign | -0.158 | Destabilizing | 0.072 | N | 0.334 | neutral | N | 0.394782049 | None | -0.424(TCAP) | N |
| T/P | 0.2174 | likely_benign | 0.3041 | benign | -0.349 | Destabilizing | 0.523 | D | 0.295 | neutral | N | 0.45383316 | None | 0.057(TCAP) | N |
| T/Q | 0.2447 | likely_benign | 0.3157 | benign | -0.332 | Destabilizing | 0.61 | D | 0.314 | neutral | None | None | None | -0.295(TCAP) | N |
| T/R | 0.226 | likely_benign | 0.3343 | benign | -0.158 | Destabilizing | 0.899 | D | 0.305 | neutral | None | None | None | -0.209(TCAP) | N |
| T/S | 0.1036 | likely_benign | 0.1206 | benign | -0.446 | Destabilizing | None | N | 0.26 | neutral | N | 0.366044193 | None | -0.183(TCAP) | N |
| T/V | 0.1593 | likely_benign | 0.2056 | benign | -0.349 | Destabilizing | 0.405 | N | 0.373 | neutral | None | None | None | 0.057(TCAP) | N |
| T/W | 0.7433 | likely_pathogenic | 0.8421 | pathogenic | -1.012 | Destabilizing | 0.995 | D | 0.489 | neutral | None | None | None | 0.07(TCAP) | N |
| T/Y | 0.4312 | ambiguous | 0.5589 | ambiguous | -0.729 | Destabilizing | 0.948 | D | 0.364 | neutral | None | None | None | 0.264(TCAP) | 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.