Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35703 | 107332;107333;107334 | chr2:178528644;178528643;178528642 | chr2:179393371;179393370;179393369 |
| N2AB | 34062 | 102409;102410;102411 | chr2:178528644;178528643;178528642 | chr2:179393371;179393370;179393369 |
| N2A | 33135 | 99628;99629;99630 | chr2:178528644;178528643;178528642 | chr2:179393371;179393370;179393369 |
| N2B | 26638 | 80137;80138;80139 | chr2:178528644;178528643;178528642 | chr2:179393371;179393370;179393369 |
| Novex-1 | 26763 | 80512;80513;80514 | chr2:178528644;178528643;178528642 | chr2:179393371;179393370;179393369 |
| Novex-2 | 26830 | 80713;80714;80715 | chr2:178528644;178528643;178528642 | chr2:179393371;179393370;179393369 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/G | rs757500242  |
-0.386 | 0.012 | N | 0.278 | 0.058 | 0.178374595973 | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 1.66722E-04 |
| A/G | rs757500242 |
-0.386 | 0.012 | N | 0.278 | 0.058 | 0.178374595973 | gnomAD-4.0.0 | 2.05389E-06 | None | None | None | None | N | None | 0 | 2.24517E-05 | None | 0 | 0 | None | 0 | 0 | 1.79959E-06 | 0 | 0 |
| A/S | None | None | None | N | 0.106 | 0.1 | 0.115124310173 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| A/V | None | None | None | N | 0.18 | 0.08 | 0.219573609325 | gnomAD-4.0.0 | 4.10778E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39876E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5708 | likely_pathogenic | 0.6145 | pathogenic | -0.658 | Destabilizing | 0.676 | D | 0.367 | neutral | None | None | None | None | N |
| A/D | 0.3012 | likely_benign | 0.3625 | ambiguous | 0.032 | Stabilizing | 0.029 | N | 0.397 | neutral | N | 0.439629308 | None | None | N |
| A/E | 0.253 | likely_benign | 0.2752 | benign | -0.009 | Destabilizing | 0.038 | N | 0.326 | neutral | None | None | None | None | N |
| A/F | 0.3431 | ambiguous | 0.3804 | ambiguous | -0.547 | Destabilizing | 0.12 | N | 0.417 | neutral | None | None | None | None | N |
| A/G | 0.177 | likely_benign | 0.1999 | benign | -0.619 | Destabilizing | 0.012 | N | 0.278 | neutral | N | 0.466546551 | None | None | N |
| A/H | 0.4686 | ambiguous | 0.4935 | ambiguous | -0.568 | Destabilizing | 0.001 | N | 0.328 | neutral | None | None | None | None | N |
| A/I | 0.2468 | likely_benign | 0.2717 | benign | 0.005 | Stabilizing | 0.013 | N | 0.345 | neutral | None | None | None | None | N |
| A/K | 0.4363 | ambiguous | 0.4443 | ambiguous | -0.602 | Destabilizing | 0.038 | N | 0.334 | neutral | None | None | None | None | N |
| A/L | 0.1963 | likely_benign | 0.2262 | benign | 0.005 | Stabilizing | 0.016 | N | 0.306 | neutral | None | None | None | None | N |
| A/M | 0.2538 | likely_benign | 0.2719 | benign | -0.209 | Destabilizing | 0.214 | N | 0.337 | neutral | None | None | None | None | N |
| A/N | 0.2441 | likely_benign | 0.272 | benign | -0.396 | Destabilizing | 0.038 | N | 0.39 | neutral | None | None | None | None | N |
| A/P | 0.6131 | likely_pathogenic | 0.7196 | pathogenic | -0.09 | Destabilizing | 0.171 | N | 0.372 | neutral | N | 0.455676196 | None | None | N |
| A/Q | 0.3294 | likely_benign | 0.3327 | benign | -0.476 | Destabilizing | 0.007 | N | 0.197 | neutral | None | None | None | None | N |
| A/R | 0.3522 | ambiguous | 0.3521 | ambiguous | -0.357 | Destabilizing | 0.072 | N | 0.387 | neutral | None | None | None | None | N |
| A/S | 0.0831 | likely_benign | 0.0887 | benign | -0.812 | Destabilizing | None | N | 0.106 | neutral | N | 0.410749196 | None | None | N |
| A/T | 0.0815 | likely_benign | 0.0892 | benign | -0.735 | Destabilizing | None | N | 0.197 | neutral | N | 0.361168524 | None | None | N |
| A/V | 0.1286 | likely_benign | 0.1406 | benign | -0.09 | Destabilizing | None | N | 0.18 | neutral | N | 0.378271418 | None | None | N |
| A/W | 0.7888 | likely_pathogenic | 0.8231 | pathogenic | -0.837 | Destabilizing | 0.864 | D | 0.436 | neutral | None | None | None | None | N |
| A/Y | 0.4871 | ambiguous | 0.5181 | ambiguous | -0.404 | Destabilizing | 0.002 | N | 0.31 | 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.