Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21649 | 65170;65171;65172 | chr2:178584696;178584695;178584694 | chr2:179449423;179449422;179449421 |
| N2AB | 20008 | 60247;60248;60249 | chr2:178584696;178584695;178584694 | chr2:179449423;179449422;179449421 |
| N2A | 19081 | 57466;57467;57468 | chr2:178584696;178584695;178584694 | chr2:179449423;179449422;179449421 |
| N2B | 12584 | 37975;37976;37977 | chr2:178584696;178584695;178584694 | chr2:179449423;179449422;179449421 |
| Novex-1 | 12709 | 38350;38351;38352 | chr2:178584696;178584695;178584694 | chr2:179449423;179449422;179449421 |
| Novex-2 | 12776 | 38551;38552;38553 | chr2:178584696;178584695;178584694 | chr2:179449423;179449422;179449421 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs1220907025  |
-0.068 | 0.337 | N | 0.511 | 0.227 | 0.475663983558 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| P/L | rs1220907025 |
-0.068 | 0.337 | N | 0.511 | 0.227 | 0.475663983558 | gnomAD-4.0.0 | 1.59196E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85979E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0754 | likely_benign | 0.0718 | benign | -0.919 | Destabilizing | 0.049 | N | 0.35 | neutral | N | 0.400150121 | None | None | N |
| P/C | 0.3728 | ambiguous | 0.3724 | ambiguous | -0.637 | Destabilizing | 0.964 | D | 0.321 | neutral | None | None | None | None | N |
| P/D | 0.2073 | likely_benign | 0.1982 | benign | -0.321 | Destabilizing | None | N | 0.116 | neutral | None | None | None | None | N |
| P/E | 0.1343 | likely_benign | 0.1302 | benign | -0.276 | Destabilizing | 0.001 | N | 0.117 | neutral | None | None | None | None | N |
| P/F | 0.4804 | ambiguous | 0.4691 | ambiguous | -0.489 | Destabilizing | 0.878 | D | 0.429 | neutral | None | None | None | None | N |
| P/G | 0.1833 | likely_benign | 0.1792 | benign | -1.248 | Destabilizing | None | N | 0.156 | neutral | None | None | None | None | N |
| P/H | 0.1516 | likely_benign | 0.1524 | benign | -0.659 | Destabilizing | 0.878 | D | 0.393 | neutral | None | None | None | None | N |
| P/I | 0.2995 | likely_benign | 0.2843 | benign | -0.117 | Destabilizing | 0.703 | D | 0.527 | neutral | None | None | None | None | N |
| P/K | 0.146 | likely_benign | 0.1437 | benign | -0.68 | Destabilizing | 0.121 | N | 0.333 | neutral | None | None | None | None | N |
| P/L | 0.1339 | likely_benign | 0.1257 | benign | -0.117 | Destabilizing | 0.337 | N | 0.511 | neutral | N | 0.4553314 | None | None | N |
| P/M | 0.263 | likely_benign | 0.2564 | benign | -0.253 | Destabilizing | 0.964 | D | 0.338 | neutral | None | None | None | None | N |
| P/N | 0.1934 | likely_benign | 0.1839 | benign | -0.639 | Destabilizing | 0.143 | N | 0.432 | neutral | None | None | None | None | N |
| P/Q | 0.099 | likely_benign | 0.0977 | benign | -0.665 | Destabilizing | 0.201 | N | 0.421 | neutral | N | 0.449309505 | None | None | N |
| P/R | 0.1309 | likely_benign | 0.1326 | benign | -0.359 | Destabilizing | 0.201 | N | 0.498 | neutral | N | 0.493022997 | None | None | N |
| P/S | 0.1038 | likely_benign | 0.0987 | benign | -1.213 | Destabilizing | 0.049 | N | 0.337 | neutral | N | 0.367808416 | None | None | N |
| P/T | 0.097 | likely_benign | 0.0919 | benign | -1.041 | Destabilizing | 0.201 | N | 0.378 | neutral | N | 0.393205506 | None | None | N |
| P/V | 0.1899 | likely_benign | 0.1808 | benign | -0.348 | Destabilizing | 0.403 | N | 0.465 | neutral | None | None | None | None | N |
| P/W | 0.5475 | ambiguous | 0.5667 | pathogenic | -0.722 | Destabilizing | 0.964 | D | 0.412 | neutral | None | None | None | None | N |
| P/Y | 0.3673 | ambiguous | 0.3685 | ambiguous | -0.365 | Destabilizing | 0.878 | D | 0.435 | 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.