Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29061 | 87406;87407;87408 | chr2:178558173;178558172;178558171 | chr2:179422900;179422899;179422898 |
| N2AB | 27420 | 82483;82484;82485 | chr2:178558173;178558172;178558171 | chr2:179422900;179422899;179422898 |
| N2A | 26493 | 79702;79703;79704 | chr2:178558173;178558172;178558171 | chr2:179422900;179422899;179422898 |
| N2B | 19996 | 60211;60212;60213 | chr2:178558173;178558172;178558171 | chr2:179422900;179422899;179422898 |
| Novex-1 | 20121 | 60586;60587;60588 | chr2:178558173;178558172;178558171 | chr2:179422900;179422899;179422898 |
| Novex-2 | 20188 | 60787;60788;60789 | chr2:178558173;178558172;178558171 | chr2:179422900;179422899;179422898 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | rs755378840  |
None | 0.994 | N | 0.496 | 0.37 | 0.223146558224 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/D | rs755378840 |
None | 0.994 | N | 0.496 | 0.37 | 0.223146558224 | gnomAD-4.0.0 | 3.09851E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23786E-06 | 0 | 0 |
| N/S | None | None | 0.978 | N | 0.525 | 0.159 | 0.136095386433 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/Y | rs755378840 |
-0.476 | 0.999 | N | 0.657 | 0.449 | 0.352262096564 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| N/Y | rs755378840 |
-0.476 | 0.999 | N | 0.657 | 0.449 | 0.352262096564 | gnomAD-4.0.0 | 6.84244E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99441E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.2499 | likely_benign | 0.2484 | benign | -0.559 | Destabilizing | 0.992 | D | 0.507 | neutral | None | None | None | None | I |
| N/C | 0.3256 | likely_benign | 0.344 | ambiguous | 0.241 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | I |
| N/D | 0.1791 | likely_benign | 0.1774 | benign | 0.103 | Stabilizing | 0.994 | D | 0.496 | neutral | N | 0.423306622 | None | None | I |
| N/E | 0.617 | likely_pathogenic | 0.6319 | pathogenic | 0.107 | Stabilizing | 0.996 | D | 0.518 | neutral | None | None | None | None | I |
| N/F | 0.6044 | likely_pathogenic | 0.6127 | pathogenic | -0.731 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| N/G | 0.3302 | likely_benign | 0.313 | benign | -0.79 | Destabilizing | 0.996 | D | 0.481 | neutral | None | None | None | None | I |
| N/H | 0.1475 | likely_benign | 0.142 | benign | -0.704 | Destabilizing | 0.999 | D | 0.563 | neutral | N | 0.508965523 | None | None | I |
| N/I | 0.2864 | likely_benign | 0.3096 | benign | -0.021 | Destabilizing | 0.997 | D | 0.705 | prob.neutral | N | 0.508965523 | None | None | I |
| N/K | 0.5744 | likely_pathogenic | 0.579 | pathogenic | 0.037 | Stabilizing | 0.994 | D | 0.517 | neutral | N | 0.435025125 | None | None | I |
| N/L | 0.2735 | likely_benign | 0.281 | benign | -0.021 | Destabilizing | 0.998 | D | 0.599 | neutral | None | None | None | None | I |
| N/M | 0.4132 | ambiguous | 0.4261 | ambiguous | 0.397 | Stabilizing | 1.0 | D | 0.632 | neutral | None | None | None | None | I |
| N/P | 0.3737 | ambiguous | 0.3696 | ambiguous | -0.172 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| N/Q | 0.4807 | ambiguous | 0.4853 | ambiguous | -0.5 | Destabilizing | 1.0 | D | 0.568 | neutral | None | None | None | None | I |
| N/R | 0.5875 | likely_pathogenic | 0.581 | pathogenic | 0.084 | Stabilizing | 0.999 | D | 0.563 | neutral | None | None | None | None | I |
| N/S | 0.0812 | likely_benign | 0.0792 | benign | -0.369 | Destabilizing | 0.978 | D | 0.525 | neutral | N | 0.436715849 | None | None | I |
| N/T | 0.1464 | likely_benign | 0.1386 | benign | -0.194 | Destabilizing | 0.543 | D | 0.217 | neutral | N | 0.398370892 | None | None | I |
| N/V | 0.2444 | likely_benign | 0.2566 | benign | -0.172 | Destabilizing | 0.998 | D | 0.6 | neutral | None | None | None | None | I |
| N/W | 0.8772 | likely_pathogenic | 0.8747 | pathogenic | -0.599 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | I |
| N/Y | 0.2517 | likely_benign | 0.2529 | benign | -0.371 | Destabilizing | 0.999 | D | 0.657 | neutral | N | 0.509138882 | None | None | I |
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.