Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6634 | 20125;20126;20127 | chr2:178727678;178727677;178727676 | chr2:179592405;179592404;179592403 |
| N2AB | 6317 | 19174;19175;19176 | chr2:178727678;178727677;178727676 | chr2:179592405;179592404;179592403 |
| N2A | 5390 | 16393;16394;16395 | chr2:178727678;178727677;178727676 | chr2:179592405;179592404;179592403 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs2079599735  |
None | 0.997 | N | 0.47 | 0.442 | 0.685574053984 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/C | rs2079599735 |
None | 0.997 | N | 0.47 | 0.442 | 0.685574053984 | gnomAD-4.0.0 | 7.10648E-06 | None | None | None | None | N | None | 1.74966E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 7.23027E-06 | 0 | 0 |
| Y/H | rs1211263186 |
-0.023 | 0.028 | N | 0.239 | 0.326 | 0.310147130316 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| Y/H | rs1211263186 |
-0.023 | 0.028 | N | 0.239 | 0.326 | 0.310147130316 | gnomAD-4.0.0 | 4.77779E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.30108E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.6082 | likely_pathogenic | 0.5882 | pathogenic | -1.646 | Destabilizing | 0.842 | D | 0.453 | neutral | None | None | None | None | N |
| Y/C | 0.2307 | likely_benign | 0.1965 | benign | -0.295 | Destabilizing | 0.997 | D | 0.47 | neutral | N | 0.485465747 | None | None | N |
| Y/D | 0.4501 | ambiguous | 0.4161 | ambiguous | 0.3 | Stabilizing | 0.934 | D | 0.453 | neutral | N | 0.476144682 | None | None | N |
| Y/E | 0.7651 | likely_pathogenic | 0.7276 | pathogenic | 0.322 | Stabilizing | 0.728 | D | 0.461 | neutral | None | None | None | None | N |
| Y/F | 0.1037 | likely_benign | 0.0921 | benign | -0.892 | Destabilizing | 0.012 | N | 0.13 | neutral | N | 0.432721978 | None | None | N |
| Y/G | 0.4976 | ambiguous | 0.4947 | ambiguous | -1.906 | Destabilizing | 0.915 | D | 0.459 | neutral | None | None | None | None | N |
| Y/H | 0.213 | likely_benign | 0.1708 | benign | -0.538 | Destabilizing | 0.028 | N | 0.239 | neutral | N | 0.490287415 | None | None | N |
| Y/I | 0.5414 | ambiguous | 0.4969 | ambiguous | -0.913 | Destabilizing | 0.904 | D | 0.437 | neutral | None | None | None | None | N |
| Y/K | 0.7116 | likely_pathogenic | 0.6678 | pathogenic | -0.287 | Destabilizing | 0.904 | D | 0.439 | neutral | None | None | None | None | N |
| Y/L | 0.4392 | ambiguous | 0.4072 | ambiguous | -0.913 | Destabilizing | 0.728 | D | 0.433 | neutral | None | None | None | None | N |
| Y/M | 0.7075 | likely_pathogenic | 0.6782 | pathogenic | -0.485 | Destabilizing | 0.974 | D | 0.433 | neutral | None | None | None | None | N |
| Y/N | 0.2696 | likely_benign | 0.2316 | benign | -0.311 | Destabilizing | 0.934 | D | 0.449 | neutral | N | 0.460772584 | None | None | N |
| Y/P | 0.667 | likely_pathogenic | 0.7104 | pathogenic | -1.144 | Destabilizing | 0.991 | D | 0.479 | neutral | None | None | None | None | N |
| Y/Q | 0.5854 | likely_pathogenic | 0.5123 | ambiguous | -0.36 | Destabilizing | 0.325 | N | 0.319 | neutral | None | None | None | None | N |
| Y/R | 0.511 | ambiguous | 0.4552 | ambiguous | 0.15 | Stabilizing | 0.949 | D | 0.46 | neutral | None | None | None | None | N |
| Y/S | 0.281 | likely_benign | 0.2596 | benign | -0.942 | Destabilizing | 0.801 | D | 0.451 | neutral | N | 0.457865565 | None | None | N |
| Y/T | 0.5718 | likely_pathogenic | 0.5336 | ambiguous | -0.828 | Destabilizing | 0.974 | D | 0.43 | neutral | None | None | None | None | N |
| Y/V | 0.4703 | ambiguous | 0.4407 | ambiguous | -1.144 | Destabilizing | 0.842 | D | 0.457 | neutral | None | None | None | None | N |
| Y/W | 0.4962 | ambiguous | 0.4664 | ambiguous | -0.68 | Destabilizing | 0.998 | D | 0.451 | 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.