Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22014 | 66265;66266;66267 | chr2:178582416;178582415;178582414 | chr2:179447143;179447142;179447141 |
| N2AB | 20373 | 61342;61343;61344 | chr2:178582416;178582415;178582414 | chr2:179447143;179447142;179447141 |
| N2A | 19446 | 58561;58562;58563 | chr2:178582416;178582415;178582414 | chr2:179447143;179447142;179447141 |
| N2B | 12949 | 39070;39071;39072 | chr2:178582416;178582415;178582414 | chr2:179447143;179447142;179447141 |
| Novex-1 | 13074 | 39445;39446;39447 | chr2:178582416;178582415;178582414 | chr2:179447143;179447142;179447141 |
| Novex-2 | 13141 | 39646;39647;39648 | chr2:178582416;178582415;178582414 | chr2:179447143;179447142;179447141 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs750531050  |
-0.242 | 0.684 | N | 0.403 | 0.204 | 0.277317399466 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| S/N | rs750531050 |
-0.242 | 0.684 | N | 0.403 | 0.204 | 0.277317399466 | gnomAD-4.0.0 | 2.05368E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.47979E-05 | 0 |
| S/R | None | None | 0.007 | N | 0.306 | 0.267 | 0.295974979623 | gnomAD-4.0.0 | 1.20039E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31258E-06 | 0 | 0 |
| S/T | rs750531050 |
-0.125 | 0.684 | N | 0.411 | 0.199 | 0.281780670237 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/T | rs750531050 |
-0.125 | 0.684 | N | 0.411 | 0.199 | 0.281780670237 | gnomAD-4.0.0 | 3.42281E-06 | None | None | None | None | N | None | 5.98372E-05 | 2.23814E-05 | None | 0 | 0 | None | 0 | 0 | 1.79952E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1007 | likely_benign | 0.0964 | benign | -0.691 | Destabilizing | 0.543 | D | 0.383 | neutral | None | None | None | None | N |
| S/C | 0.1522 | likely_benign | 0.1397 | benign | -0.353 | Destabilizing | 0.994 | D | 0.523 | neutral | N | 0.490125512 | None | None | N |
| S/D | 0.5897 | likely_pathogenic | 0.5927 | pathogenic | 0.121 | Stabilizing | 0.004 | N | 0.192 | neutral | None | None | None | None | N |
| S/E | 0.6035 | likely_pathogenic | 0.6388 | pathogenic | 0.189 | Stabilizing | 0.373 | N | 0.384 | neutral | None | None | None | None | N |
| S/F | 0.2437 | likely_benign | 0.2512 | benign | -0.836 | Destabilizing | 0.984 | D | 0.583 | neutral | None | None | None | None | N |
| S/G | 0.1588 | likely_benign | 0.1348 | benign | -0.993 | Destabilizing | 0.472 | N | 0.389 | neutral | N | 0.486553886 | None | None | N |
| S/H | 0.3606 | ambiguous | 0.3486 | ambiguous | -1.318 | Destabilizing | 0.953 | D | 0.521 | neutral | None | None | None | None | N |
| S/I | 0.2434 | likely_benign | 0.2261 | benign | 0.022 | Stabilizing | 0.939 | D | 0.574 | neutral | N | 0.4804775 | None | None | N |
| S/K | 0.7537 | likely_pathogenic | 0.7492 | pathogenic | -0.2 | Destabilizing | 0.037 | N | 0.18 | neutral | None | None | None | None | N |
| S/L | 0.1664 | likely_benign | 0.1558 | benign | 0.022 | Stabilizing | 0.742 | D | 0.489 | neutral | None | None | None | None | N |
| S/M | 0.2131 | likely_benign | 0.2029 | benign | 0.029 | Stabilizing | 0.984 | D | 0.521 | neutral | None | None | None | None | N |
| S/N | 0.1962 | likely_benign | 0.169 | benign | -0.413 | Destabilizing | 0.684 | D | 0.403 | neutral | N | 0.47836855 | None | None | N |
| S/P | 0.9685 | likely_pathogenic | 0.9579 | pathogenic | -0.181 | Destabilizing | 0.984 | D | 0.515 | neutral | None | None | None | None | N |
| S/Q | 0.5072 | ambiguous | 0.4896 | ambiguous | -0.372 | Destabilizing | 0.742 | D | 0.438 | neutral | None | None | None | None | N |
| S/R | 0.6758 | likely_pathogenic | 0.6656 | pathogenic | -0.302 | Destabilizing | 0.007 | N | 0.306 | neutral | N | 0.48433173 | None | None | N |
| S/T | 0.0785 | likely_benign | 0.0775 | benign | -0.388 | Destabilizing | 0.684 | D | 0.411 | neutral | N | 0.490833628 | None | None | N |
| S/V | 0.2107 | likely_benign | 0.1983 | benign | -0.181 | Destabilizing | 0.854 | D | 0.536 | neutral | None | None | None | None | N |
| S/W | 0.4642 | ambiguous | 0.506 | ambiguous | -0.881 | Destabilizing | 0.996 | D | 0.663 | neutral | None | None | None | None | N |
| S/Y | 0.2256 | likely_benign | 0.2476 | benign | -0.524 | Destabilizing | 0.984 | D | 0.582 | 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.