Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28765 | 86518;86519;86520 | chr2:178559839;178559838;178559837 | chr2:179424566;179424565;179424564 |
| N2AB | 27124 | 81595;81596;81597 | chr2:178559839;178559838;178559837 | chr2:179424566;179424565;179424564 |
| N2A | 26197 | 78814;78815;78816 | chr2:178559839;178559838;178559837 | chr2:179424566;179424565;179424564 |
| N2B | 19700 | 59323;59324;59325 | chr2:178559839;178559838;178559837 | chr2:179424566;179424565;179424564 |
| Novex-1 | 19825 | 59698;59699;59700 | chr2:178559839;178559838;178559837 | chr2:179424566;179424565;179424564 |
| Novex-2 | 19892 | 59899;59900;59901 | chr2:178559839;178559838;178559837 | chr2:179424566;179424565;179424564 |
| 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/F | rs1216320411  |
-0.643 | 0.627 | N | 0.346 | 0.29 | 0.576245406411 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| I/F | rs1216320411 |
-0.643 | 0.627 | N | 0.346 | 0.29 | 0.576245406411 | gnomAD-4.0.0 | 1.59823E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.0259E-05 |
| I/T | rs1553561335 |
None | 0.006 | N | 0.247 | 0.177 | 0.546736107678 | gnomAD-4.0.0 | 6.16952E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.09597E-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 | 0.334 | likely_benign | 0.2836 | benign | -1.214 | Destabilizing | 0.116 | N | 0.319 | neutral | None | None | None | None | I |
| I/C | 0.7344 | likely_pathogenic | 0.702 | pathogenic | -0.878 | Destabilizing | 0.944 | D | 0.386 | neutral | None | None | None | None | I |
| I/D | 0.8698 | likely_pathogenic | 0.8234 | pathogenic | -0.67 | Destabilizing | 0.818 | D | 0.455 | neutral | None | None | None | None | I |
| I/E | 0.7426 | likely_pathogenic | 0.6789 | pathogenic | -0.675 | Destabilizing | 0.818 | D | 0.451 | neutral | None | None | None | None | I |
| I/F | 0.2463 | likely_benign | 0.2106 | benign | -0.768 | Destabilizing | 0.627 | D | 0.346 | neutral | N | 0.49977134 | None | None | I |
| I/G | 0.7769 | likely_pathogenic | 0.7316 | pathogenic | -1.5 | Destabilizing | 0.69 | D | 0.439 | neutral | None | None | None | None | I |
| I/H | 0.596 | likely_pathogenic | 0.544 | ambiguous | -0.614 | Destabilizing | 0.981 | D | 0.459 | neutral | None | None | None | None | I |
| I/K | 0.6074 | likely_pathogenic | 0.5497 | ambiguous | -0.924 | Destabilizing | 0.69 | D | 0.452 | neutral | None | None | None | None | I |
| I/L | 0.134 | likely_benign | 0.1252 | benign | -0.522 | Destabilizing | 0.001 | N | 0.189 | neutral | N | 0.490114057 | None | None | I |
| I/M | 0.1265 | likely_benign | 0.1189 | benign | -0.553 | Destabilizing | 0.627 | D | 0.387 | neutral | N | 0.503293998 | None | None | I |
| I/N | 0.4167 | ambiguous | 0.374 | ambiguous | -0.823 | Destabilizing | 0.627 | D | 0.459 | neutral | N | 0.508353101 | None | None | I |
| I/P | 0.8316 | likely_pathogenic | 0.8153 | pathogenic | -0.721 | Destabilizing | 0.818 | D | 0.457 | neutral | None | None | None | None | I |
| I/Q | 0.5592 | ambiguous | 0.5101 | ambiguous | -0.957 | Destabilizing | 0.818 | D | 0.459 | neutral | None | None | None | None | I |
| I/R | 0.4851 | ambiguous | 0.4225 | ambiguous | -0.352 | Destabilizing | 0.818 | D | 0.456 | neutral | None | None | None | None | I |
| I/S | 0.3707 | ambiguous | 0.3159 | benign | -1.373 | Destabilizing | 0.193 | N | 0.409 | neutral | N | 0.490863418 | None | None | I |
| I/T | 0.1414 | likely_benign | 0.1227 | benign | -1.258 | Destabilizing | 0.006 | N | 0.247 | neutral | N | 0.416096301 | None | None | I |
| I/V | 0.0739 | likely_benign | 0.0674 | benign | -0.721 | Destabilizing | 0.001 | N | 0.191 | neutral | N | 0.416576303 | None | None | I |
| I/W | 0.8446 | likely_pathogenic | 0.8191 | pathogenic | -0.837 | Destabilizing | 0.981 | D | 0.569 | neutral | None | None | None | None | I |
| I/Y | 0.6417 | likely_pathogenic | 0.6031 | pathogenic | -0.612 | Destabilizing | 0.818 | D | 0.372 | neutral | None | None | 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.