Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20466 | 61621;61622;61623 | chr2:178590329;178590328;178590327 | chr2:179455056;179455055;179455054 |
| N2AB | 18825 | 56698;56699;56700 | chr2:178590329;178590328;178590327 | chr2:179455056;179455055;179455054 |
| N2A | 17898 | 53917;53918;53919 | chr2:178590329;178590328;178590327 | chr2:179455056;179455055;179455054 |
| N2B | 11401 | 34426;34427;34428 | chr2:178590329;178590328;178590327 | chr2:179455056;179455055;179455054 |
| Novex-1 | 11526 | 34801;34802;34803 | chr2:178590329;178590328;178590327 | chr2:179455056;179455055;179455054 |
| Novex-2 | 11593 | 35002;35003;35004 | chr2:178590329;178590328;178590327 | chr2:179455056;179455055;179455054 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/S | None | None | 0.22 | N | 0.471 | 0.178 | 0.574091456918 | gnomAD-4.0.0 | 7.04896E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.16209E-06 | 0 | 0 |
| I/T | rs372745397  |
-0.898 | 0.008 | N | 0.337 | 0.103 | None | gnomAD-2.1.1 | 9.43E-06 | None | None | None | None | N | None | 1.32926E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs372745397 |
-0.898 | 0.008 | N | 0.337 | 0.103 | None | gnomAD-4.0.0 | 2.11469E-06 | None | None | None | None | N | None | 0 | 2.4914E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.41869E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2345 | likely_benign | 0.2289 | benign | -1.025 | Destabilizing | 0.134 | N | 0.503 | neutral | None | None | None | None | N |
| I/C | 0.6371 | likely_pathogenic | 0.6044 | pathogenic | -0.78 | Destabilizing | 0.984 | D | 0.415 | neutral | None | None | None | None | N |
| I/D | 0.7235 | likely_pathogenic | 0.6607 | pathogenic | -0.195 | Destabilizing | 0.842 | D | 0.541 | neutral | None | None | None | None | N |
| I/E | 0.4961 | ambiguous | 0.4366 | ambiguous | -0.234 | Destabilizing | 0.842 | D | 0.547 | neutral | None | None | None | None | N |
| I/F | 0.1451 | likely_benign | 0.1275 | benign | -0.689 | Destabilizing | 0.498 | N | 0.375 | neutral | N | 0.462171654 | None | None | N |
| I/G | 0.6606 | likely_pathogenic | 0.6344 | pathogenic | -1.279 | Destabilizing | 0.603 | D | 0.551 | neutral | None | None | None | None | N |
| I/H | 0.4553 | ambiguous | 0.3998 | ambiguous | -0.429 | Destabilizing | 0.984 | D | 0.499 | neutral | None | None | None | None | N |
| I/K | 0.3607 | ambiguous | 0.2921 | benign | -0.614 | Destabilizing | 0.842 | D | 0.543 | neutral | None | None | None | None | N |
| I/L | 0.0894 | likely_benign | 0.0817 | benign | -0.443 | Destabilizing | None | N | 0.081 | neutral | N | 0.40358471 | None | None | N |
| I/M | 0.0902 | likely_benign | 0.0885 | benign | -0.436 | Destabilizing | 0.664 | D | 0.458 | neutral | N | 0.494841433 | None | None | N |
| I/N | 0.318 | likely_benign | 0.2822 | benign | -0.434 | Destabilizing | 0.8 | D | 0.565 | neutral | N | 0.505365071 | None | None | N |
| I/P | 0.6088 | likely_pathogenic | 0.5576 | ambiguous | -0.603 | Destabilizing | 0.942 | D | 0.564 | neutral | None | None | None | None | N |
| I/Q | 0.3584 | ambiguous | 0.3054 | benign | -0.613 | Destabilizing | 0.942 | D | 0.549 | neutral | None | None | None | None | N |
| I/R | 0.2996 | likely_benign | 0.2332 | benign | -0.054 | Destabilizing | 0.842 | D | 0.576 | neutral | None | None | None | None | N |
| I/S | 0.2921 | likely_benign | 0.2579 | benign | -1.034 | Destabilizing | 0.22 | N | 0.471 | neutral | N | 0.493281208 | None | None | N |
| I/T | 0.1171 | likely_benign | 0.1155 | benign | -0.956 | Destabilizing | 0.008 | N | 0.337 | neutral | N | 0.42130368 | None | None | N |
| I/V | 0.0717 | likely_benign | 0.0775 | benign | -0.603 | Destabilizing | 0.001 | N | 0.101 | neutral | N | 0.398197533 | None | None | N |
| I/W | 0.6477 | likely_pathogenic | 0.5821 | pathogenic | -0.701 | Destabilizing | 0.984 | D | 0.564 | neutral | None | None | None | None | N |
| I/Y | 0.4795 | ambiguous | 0.3969 | ambiguous | -0.475 | Destabilizing | 0.842 | D | 0.489 | 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.