Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30514 | 91765;91766;91767 | chr2:178550991;178550990;178550989 | chr2:179415718;179415717;179415716 |
| N2AB | 28873 | 86842;86843;86844 | chr2:178550991;178550990;178550989 | chr2:179415718;179415717;179415716 |
| N2A | 27946 | 84061;84062;84063 | chr2:178550991;178550990;178550989 | chr2:179415718;179415717;179415716 |
| N2B | 21449 | 64570;64571;64572 | chr2:178550991;178550990;178550989 | chr2:179415718;179415717;179415716 |
| Novex-1 | 21574 | 64945;64946;64947 | chr2:178550991;178550990;178550989 | chr2:179415718;179415717;179415716 |
| Novex-2 | 21641 | 65146;65147;65148 | chr2:178550991;178550990;178550989 | chr2:179415718;179415717;179415716 |
| 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/T | rs1699214522  |
None | 0.006 | N | 0.343 | 0.125 | 0.489311470972 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1699214522 |
None | 0.006 | N | 0.343 | 0.125 | 0.489311470972 | gnomAD-4.0.0 | 6.5722E-06 | None | None | None | None | N | None | 2.41336E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1056281241 |
-0.791 | None | N | 0.085 | 0.082 | 0.298403945805 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| I/V | rs1056281241 |
-0.791 | None | N | 0.085 | 0.082 | 0.298403945805 | gnomAD-4.0.0 | 1.59292E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8603E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2381 | likely_benign | 0.2762 | benign | -0.828 | Destabilizing | 0.007 | N | 0.315 | neutral | None | None | None | None | N |
| I/C | 0.3896 | ambiguous | 0.4588 | ambiguous | -0.74 | Destabilizing | 0.204 | N | 0.363 | neutral | None | None | None | None | N |
| I/D | 0.58 | likely_pathogenic | 0.6055 | pathogenic | -0.109 | Destabilizing | 0.068 | N | 0.664 | prob.neutral | None | None | None | None | N |
| I/E | 0.5381 | ambiguous | 0.5312 | ambiguous | -0.182 | Destabilizing | 0.068 | N | 0.617 | neutral | None | None | None | None | N |
| I/F | 0.0753 | likely_benign | 0.1075 | benign | -0.696 | Destabilizing | None | N | 0.138 | neutral | N | 0.428278085 | None | None | N |
| I/G | 0.4567 | ambiguous | 0.5302 | ambiguous | -1.022 | Destabilizing | 0.068 | N | 0.569 | neutral | None | None | None | None | N |
| I/H | 0.3387 | likely_benign | 0.3909 | ambiguous | -0.216 | Destabilizing | 0.112 | N | 0.545 | neutral | None | None | None | None | N |
| I/K | 0.4397 | ambiguous | 0.4455 | ambiguous | -0.434 | Destabilizing | 0.035 | N | 0.601 | neutral | None | None | None | None | N |
| I/L | 0.0818 | likely_benign | 0.1035 | benign | -0.429 | Destabilizing | None | N | 0.085 | neutral | N | 0.395648379 | None | None | N |
| I/M | 0.0811 | likely_benign | 0.1004 | benign | -0.465 | Destabilizing | 0.046 | N | 0.378 | neutral | N | 0.449810937 | None | None | N |
| I/N | 0.1701 | likely_benign | 0.1934 | benign | -0.263 | Destabilizing | 0.162 | N | 0.653 | prob.neutral | N | 0.442442248 | None | None | N |
| I/P | 0.4135 | ambiguous | 0.4549 | ambiguous | -0.528 | Destabilizing | 0.439 | N | 0.635 | neutral | None | None | None | None | N |
| I/Q | 0.3575 | ambiguous | 0.3775 | ambiguous | -0.474 | Destabilizing | 0.204 | N | 0.64 | neutral | None | None | None | None | N |
| I/R | 0.3461 | ambiguous | 0.3677 | ambiguous | 0.13 | Stabilizing | 0.204 | N | 0.653 | prob.neutral | None | None | None | None | N |
| I/S | 0.1993 | likely_benign | 0.2341 | benign | -0.79 | Destabilizing | 0.026 | N | 0.463 | neutral | N | 0.390301274 | None | None | N |
| I/T | 0.1902 | likely_benign | 0.222 | benign | -0.748 | Destabilizing | 0.006 | N | 0.343 | neutral | N | 0.360941159 | None | None | N |
| I/V | 0.067 | likely_benign | 0.0694 | benign | -0.528 | Destabilizing | None | N | 0.085 | neutral | N | 0.41132712 | None | None | N |
| I/W | 0.5761 | likely_pathogenic | 0.6778 | pathogenic | -0.687 | Destabilizing | 0.204 | N | 0.495 | neutral | None | None | None | None | N |
| I/Y | 0.2079 | likely_benign | 0.2737 | benign | -0.451 | Destabilizing | None | N | 0.147 | 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.