Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17324 | 52195;52196;52197 | chr2:178609340;178609339;178609338 | chr2:179474067;179474066;179474065 |
| N2AB | 15683 | 47272;47273;47274 | chr2:178609340;178609339;178609338 | chr2:179474067;179474066;179474065 |
| N2A | 14756 | 44491;44492;44493 | chr2:178609340;178609339;178609338 | chr2:179474067;179474066;179474065 |
| N2B | 8259 | 25000;25001;25002 | chr2:178609340;178609339;178609338 | chr2:179474067;179474066;179474065 |
| Novex-1 | 8384 | 25375;25376;25377 | chr2:178609340;178609339;178609338 | chr2:179474067;179474066;179474065 |
| Novex-2 | 8451 | 25576;25577;25578 | chr2:178609340;178609339;178609338 | chr2:179474067;179474066;179474065 |
| 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 | rs755536501  |
-2.529 | 0.801 | D | 0.808 | 0.39 | 0.674832526739 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs755536501 |
-2.529 | 0.801 | D | 0.808 | 0.39 | 0.674832526739 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs755536501 |
-2.529 | 0.801 | D | 0.808 | 0.39 | 0.674832526739 | gnomAD-4.0.0 | 6.20585E-06 | None | None | None | None | N | None | 4.01467E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.24185E-06 | 1.10127E-05 | 1.60426E-05 |
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 | 0.4367 | ambiguous | 0.4402 | ambiguous | -2.058 | Highly Destabilizing | 0.525 | D | 0.686 | prob.neutral | None | None | None | None | N |
| I/C | 0.7428 | likely_pathogenic | 0.7932 | pathogenic | -1.282 | Destabilizing | 0.998 | D | 0.841 | deleterious | None | None | None | None | N |
| I/D | 0.9483 | likely_pathogenic | 0.9451 | pathogenic | -1.64 | Destabilizing | 0.991 | D | 0.88 | deleterious | None | None | None | None | N |
| I/E | 0.8235 | likely_pathogenic | 0.8157 | pathogenic | -1.536 | Destabilizing | 0.974 | D | 0.867 | deleterious | None | None | None | None | N |
| I/F | 0.198 | likely_benign | 0.196 | benign | -1.336 | Destabilizing | 0.801 | D | 0.735 | prob.delet. | N | 0.485709691 | None | None | N |
| I/G | 0.8706 | likely_pathogenic | 0.8774 | pathogenic | -2.495 | Highly Destabilizing | 0.974 | D | 0.862 | deleterious | None | None | None | None | N |
| I/H | 0.7663 | likely_pathogenic | 0.7815 | pathogenic | -1.767 | Destabilizing | 0.998 | D | 0.855 | deleterious | None | None | None | None | N |
| I/K | 0.6209 | likely_pathogenic | 0.6431 | pathogenic | -1.418 | Destabilizing | 0.974 | D | 0.861 | deleterious | None | None | None | None | N |
| I/L | 0.158 | likely_benign | 0.173 | benign | -0.867 | Destabilizing | 0.005 | N | 0.22 | neutral | D | 0.523919986 | None | None | N |
| I/M | 0.1269 | likely_benign | 0.1359 | benign | -0.699 | Destabilizing | 0.136 | N | 0.356 | neutral | N | 0.486341574 | None | None | N |
| I/N | 0.7293 | likely_pathogenic | 0.7175 | pathogenic | -1.41 | Destabilizing | 0.989 | D | 0.875 | deleterious | D | 0.52698431 | None | None | N |
| I/P | 0.9428 | likely_pathogenic | 0.9395 | pathogenic | -1.236 | Destabilizing | 0.991 | D | 0.88 | deleterious | None | None | None | None | N |
| I/Q | 0.6982 | likely_pathogenic | 0.7255 | pathogenic | -1.45 | Destabilizing | 0.974 | D | 0.877 | deleterious | None | None | None | None | N |
| I/R | 0.5261 | ambiguous | 0.5345 | ambiguous | -0.966 | Destabilizing | 0.974 | D | 0.881 | deleterious | None | None | None | None | N |
| I/S | 0.5855 | likely_pathogenic | 0.575 | pathogenic | -2.109 | Highly Destabilizing | 0.891 | D | 0.81 | deleterious | N | 0.503346647 | None | None | N |
| I/T | 0.2912 | likely_benign | 0.3022 | benign | -1.868 | Destabilizing | 0.801 | D | 0.808 | deleterious | D | 0.536601282 | None | None | N |
| I/V | 0.0779 | likely_benign | 0.0824 | benign | -1.236 | Destabilizing | 0.005 | N | 0.187 | neutral | N | 0.503560569 | None | None | N |
| I/W | 0.787 | likely_pathogenic | 0.8253 | pathogenic | -1.534 | Destabilizing | 0.998 | D | 0.844 | deleterious | None | None | None | None | N |
| I/Y | 0.6173 | likely_pathogenic | 0.6148 | pathogenic | -1.265 | Destabilizing | 0.991 | D | 0.875 | deleterious | 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.