Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1544 | 4855;4856;4857 | chr2:178777435;178777434;178777433 | chr2:179642162;179642161;179642160 |
| N2AB | 1544 | 4855;4856;4857 | chr2:178777435;178777434;178777433 | chr2:179642162;179642161;179642160 |
| N2A | 1544 | 4855;4856;4857 | chr2:178777435;178777434;178777433 | chr2:179642162;179642161;179642160 |
| N2B | 1498 | 4717;4718;4719 | chr2:178777435;178777434;178777433 | chr2:179642162;179642161;179642160 |
| Novex-1 | 1498 | 4717;4718;4719 | chr2:178777435;178777434;178777433 | chr2:179642162;179642161;179642160 |
| Novex-2 | 1498 | 4717;4718;4719 | chr2:178777435;178777434;178777433 | chr2:179642162;179642161;179642160 |
| Novex-3 | 1544 | 4855;4856;4857 | chr2:178777435;178777434;178777433 | chr2:179642162;179642161;179642160 |
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/V | rs72647877  |
-0.587 | 0.001 | N | 0.167 | 0.065 | None | gnomAD-2.1.1 | 5.63032E-03 | None | None | None | None | N | None | 3.44035E-02 | 4.38671E-03 | None | 3.36752E-02 | 0 | None | 6.86454E-04 | None | 3.99E-05 | 1.23988E-03 | 6.55875E-03 |
| I/V | rs72647877 |
-0.587 | 0.001 | N | 0.167 | 0.065 | None | gnomAD-3.1.2 | 1.16702E-02 | None | None | None | None | N | None | 3.49146E-02 | 6.87173E-03 | 0 | 3.88825E-02 | 0 | None | 0 | 9.49367E-03 | 9.26089E-04 | 6.21118E-04 | 9.57854E-03 |
| I/V | rs72647877 |
-0.587 | 0.001 | N | 0.167 | 0.065 | None | 1000 genomes | 1.19808E-02 | None | None | None | None | N | None | 4.39E-02 | 2.9E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/V | rs72647877 |
-0.587 | 0.001 | N | 0.167 | 0.065 | None | gnomAD-4.0.0 | 3.45281E-03 | None | None | None | None | N | None | 3.6533E-02 | 5.48406E-03 | None | 3.51061E-02 | 0 | None | 0 | 1.23844E-02 | 7.86533E-04 | 7.1369E-04 | 6.32222E-03 |
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 | 0.101 | likely_benign | 0.122 | benign | -1.33 | Destabilizing | 0.001 | N | 0.231 | neutral | None | None | None | None | N |
| I/C | 0.3811 | ambiguous | 0.4137 | ambiguous | -0.973 | Destabilizing | 0.132 | N | 0.525 | neutral | None | None | None | None | N |
| I/D | 0.2465 | likely_benign | 0.2746 | benign | -0.27 | Destabilizing | None | N | 0.319 | neutral | None | None | None | None | N |
| I/E | 0.2347 | likely_benign | 0.2673 | benign | -0.271 | Destabilizing | 0.002 | N | 0.365 | neutral | None | None | None | None | N |
| I/F | 0.0997 | likely_benign | 0.1023 | benign | -0.873 | Destabilizing | None | N | 0.109 | neutral | N | 0.419219998 | None | None | N |
| I/G | 0.2607 | likely_benign | 0.3141 | benign | -1.634 | Destabilizing | 0.002 | N | 0.361 | neutral | None | None | None | None | N |
| I/H | 0.1641 | likely_benign | 0.1803 | benign | -0.779 | Destabilizing | 0.132 | N | 0.611 | neutral | None | None | None | None | N |
| I/K | 0.1262 | likely_benign | 0.1363 | benign | -0.737 | Destabilizing | 0.002 | N | 0.377 | neutral | None | None | None | None | N |
| I/L | 0.0768 | likely_benign | 0.0793 | benign | -0.588 | Destabilizing | None | N | 0.111 | neutral | N | 0.435484857 | None | None | N |
| I/M | 0.0653 | likely_benign | 0.0683 | benign | -0.559 | Destabilizing | None | N | 0.153 | neutral | N | 0.447718976 | None | None | N |
| I/N | 0.0663 | likely_benign | 0.073 | benign | -0.574 | Destabilizing | None | N | 0.324 | neutral | N | 0.422207892 | None | None | N |
| I/P | 0.357 | ambiguous | 0.4092 | ambiguous | -0.802 | Destabilizing | 0.018 | N | 0.533 | neutral | None | None | None | None | N |
| I/Q | 0.1537 | likely_benign | 0.1708 | benign | -0.721 | Destabilizing | None | N | 0.345 | neutral | None | None | None | None | N |
| I/R | 0.1167 | likely_benign | 0.1183 | benign | -0.235 | Destabilizing | 0.009 | N | 0.475 | neutral | None | None | None | None | N |
| I/S | 0.0839 | likely_benign | 0.0969 | benign | -1.28 | Destabilizing | 0.001 | N | 0.365 | neutral | N | 0.332629075 | None | None | N |
| I/T | 0.058 | likely_benign | 0.0647 | benign | -1.156 | Destabilizing | None | N | 0.153 | neutral | N | 0.310769438 | None | None | N |
| I/V | 0.0685 | likely_benign | 0.0654 | benign | -0.802 | Destabilizing | 0.001 | N | 0.167 | neutral | N | 0.412468934 | None | None | N |
| I/W | 0.5508 | ambiguous | 0.5647 | pathogenic | -0.886 | Destabilizing | 0.316 | N | 0.579 | neutral | None | None | None | None | N |
| I/Y | 0.2565 | likely_benign | 0.2675 | benign | -0.65 | Destabilizing | 0.004 | N | 0.522 | 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.