Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22503 | 67732;67733;67734 | chr2:178579690;178579689;178579688 | chr2:179444417;179444416;179444415 |
| N2AB | 20862 | 62809;62810;62811 | chr2:178579690;178579689;178579688 | chr2:179444417;179444416;179444415 |
| N2A | 19935 | 60028;60029;60030 | chr2:178579690;178579689;178579688 | chr2:179444417;179444416;179444415 |
| N2B | 13438 | 40537;40538;40539 | chr2:178579690;178579689;178579688 | chr2:179444417;179444416;179444415 |
| Novex-1 | 13563 | 40912;40913;40914 | chr2:178579690;178579689;178579688 | chr2:179444417;179444416;179444415 |
| Novex-2 | 13630 | 41113;41114;41115 | chr2:178579690;178579689;178579688 | chr2:179444417;179444416;179444415 |
| 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/F | None | None | 0.773 | N | 0.561 | 0.311 | 0.672880393974 | gnomAD-4.0.0 | 6.84396E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65739E-05 |
| S/P | None | None | 0.773 | N | 0.506 | 0.202 | 0.296679040009 | 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 |
| S/Y | None | None | 0.912 | D | 0.535 | 0.328 | 0.682517699708 | gnomAD-4.0.0 | 2.73758E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59868E-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 | 0.093 | likely_benign | 0.1097 | benign | -0.381 | Destabilizing | 0.001 | N | 0.137 | neutral | N | 0.496644879 | None | None | N |
| S/C | 0.1129 | likely_benign | 0.1211 | benign | -0.302 | Destabilizing | 0.928 | D | 0.462 | neutral | N | 0.501533411 | None | None | N |
| S/D | 0.4342 | ambiguous | 0.5334 | ambiguous | 0.592 | Stabilizing | 0.563 | D | 0.509 | neutral | None | None | None | None | N |
| S/E | 0.6128 | likely_pathogenic | 0.7186 | pathogenic | 0.536 | Stabilizing | 0.388 | N | 0.477 | neutral | None | None | None | None | N |
| S/F | 0.3095 | likely_benign | 0.393 | ambiguous | -0.797 | Destabilizing | 0.773 | D | 0.561 | neutral | N | 0.505227077 | None | None | N |
| S/G | 0.0927 | likely_benign | 0.1024 | benign | -0.546 | Destabilizing | None | N | 0.117 | neutral | None | None | None | None | N |
| S/H | 0.4414 | ambiguous | 0.4972 | ambiguous | -0.925 | Destabilizing | 0.981 | D | 0.468 | neutral | None | None | None | None | N |
| S/I | 0.2507 | likely_benign | 0.2986 | benign | -0.073 | Destabilizing | 0.69 | D | 0.524 | neutral | None | None | None | None | N |
| S/K | 0.7793 | likely_pathogenic | 0.8566 | pathogenic | -0.304 | Destabilizing | 0.388 | N | 0.497 | neutral | None | None | None | None | N |
| S/L | 0.1616 | likely_benign | 0.201 | benign | -0.073 | Destabilizing | 0.241 | N | 0.474 | neutral | None | None | None | None | N |
| S/M | 0.2531 | likely_benign | 0.2902 | benign | -0.007 | Destabilizing | 0.944 | D | 0.468 | neutral | None | None | None | None | N |
| S/N | 0.1801 | likely_benign | 0.2001 | benign | -0.124 | Destabilizing | 0.388 | N | 0.531 | neutral | None | None | None | None | N |
| S/P | 0.6318 | likely_pathogenic | 0.7513 | pathogenic | -0.144 | Destabilizing | 0.773 | D | 0.506 | neutral | N | 0.495140582 | None | None | N |
| S/Q | 0.6175 | likely_pathogenic | 0.6885 | pathogenic | -0.282 | Destabilizing | 0.818 | D | 0.533 | neutral | None | None | None | None | N |
| S/R | 0.7538 | likely_pathogenic | 0.844 | pathogenic | -0.181 | Destabilizing | 0.69 | D | 0.506 | neutral | None | None | None | None | N |
| S/T | 0.0921 | likely_benign | 0.0974 | benign | -0.251 | Destabilizing | 0.324 | N | 0.465 | neutral | N | 0.442157033 | None | None | N |
| S/V | 0.2092 | likely_benign | 0.253 | benign | -0.144 | Destabilizing | 0.241 | N | 0.483 | neutral | None | None | None | None | N |
| S/W | 0.5242 | ambiguous | 0.6307 | pathogenic | -0.79 | Destabilizing | 0.981 | D | 0.606 | neutral | None | None | None | None | N |
| S/Y | 0.2535 | likely_benign | 0.3183 | benign | -0.497 | Destabilizing | 0.912 | D | 0.535 | neutral | D | 0.524428913 | 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.