Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9762 | 29509;29510;29511 | chr2:178706590;178706589;178706588 | chr2:179571317;179571316;179571315 |
| N2AB | 9445 | 28558;28559;28560 | chr2:178706590;178706589;178706588 | chr2:179571317;179571316;179571315 |
| N2A | 8518 | 25777;25778;25779 | chr2:178706590;178706589;178706588 | chr2:179571317;179571316;179571315 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs1347223686  |
0.024 | 0.1 | None | 0.307 | 0.235 | 0.389596023526 | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | I | None | 0 | 0 | None | 9.93E-05 | 5.56E-05 | None | 0 | None | 0 | 8.85E-06 | 0 |
| T/I | rs1347223686 |
0.024 | 0.1 | None | 0.307 | 0.235 | 0.389596023526 | gnomAD-4.0.0 | 2.73664E-06 | None | None | None | None | I | None | 0 | 0 | None | 3.82673E-05 | 2.51915E-05 | None | 0 | 0 | 1.79885E-06 | 0 | 0 |
| T/K | None | None | 0.982 | None | 0.465 | 0.34 | 0.456919554969 | gnomAD-4.0.0 | 1.36832E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79885E-06 | 0 | 0 |
| T/R | None | None | 0.991 | None | 0.512 | 0.362 | 0.614442799871 | gnomAD-4.0.0 | 6.84159E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99423E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.321 | likely_benign | 0.2099 | benign | -0.652 | Destabilizing | 0.76 | D | 0.467 | neutral | None | None | None | None | I |
| T/C | 0.9034 | likely_pathogenic | 0.815 | pathogenic | -0.566 | Destabilizing | 0.999 | D | 0.548 | neutral | None | None | None | None | I |
| T/D | 0.9121 | likely_pathogenic | 0.7881 | pathogenic | -1.056 | Destabilizing | 0.986 | D | 0.464 | neutral | None | None | None | None | I |
| T/E | 0.8789 | likely_pathogenic | 0.7221 | pathogenic | -1.074 | Destabilizing | 0.986 | D | 0.463 | neutral | None | None | None | None | I |
| T/F | 0.8653 | likely_pathogenic | 0.7085 | pathogenic | -1.027 | Destabilizing | 0.986 | D | 0.613 | neutral | None | None | None | None | I |
| T/G | 0.5625 | ambiguous | 0.4542 | ambiguous | -0.858 | Destabilizing | 0.953 | D | 0.523 | neutral | None | None | None | None | I |
| T/H | 0.8216 | likely_pathogenic | 0.672 | pathogenic | -1.261 | Destabilizing | 0.999 | D | 0.623 | neutral | None | None | None | None | I |
| T/I | 0.7706 | likely_pathogenic | 0.5845 | pathogenic | -0.202 | Destabilizing | 0.1 | N | 0.307 | neutral | None | None | None | None | I |
| T/K | 0.6772 | likely_pathogenic | 0.4412 | ambiguous | -0.683 | Destabilizing | 0.982 | D | 0.465 | neutral | None | None | None | None | I |
| T/L | 0.4304 | ambiguous | 0.2918 | benign | -0.202 | Destabilizing | 0.91 | D | 0.443 | neutral | None | None | None | None | I |
| T/M | 0.3732 | ambiguous | 0.2422 | benign | 0.277 | Stabilizing | 0.996 | D | 0.531 | neutral | None | None | None | None | I |
| T/N | 0.5107 | ambiguous | 0.3506 | ambiguous | -0.788 | Destabilizing | 0.986 | D | 0.488 | neutral | None | None | None | None | I |
| T/P | 0.8237 | likely_pathogenic | 0.632 | pathogenic | -0.322 | Destabilizing | 0.991 | D | 0.511 | neutral | None | None | None | None | I |
| T/Q | 0.6527 | likely_pathogenic | 0.4776 | ambiguous | -1.107 | Destabilizing | 0.993 | D | 0.519 | neutral | None | None | None | None | I |
| T/R | 0.6324 | likely_pathogenic | 0.3701 | ambiguous | -0.331 | Destabilizing | 0.991 | D | 0.512 | neutral | None | None | None | None | I |
| T/S | 0.2824 | likely_benign | 0.21 | benign | -0.917 | Destabilizing | 0.17 | N | 0.365 | neutral | None | None | None | None | I |
| T/V | 0.5385 | ambiguous | 0.3992 | ambiguous | -0.322 | Destabilizing | 0.91 | D | 0.447 | neutral | None | None | None | None | I |
| T/W | 0.9659 | likely_pathogenic | 0.91 | pathogenic | -1.007 | Destabilizing | 0.999 | D | 0.668 | neutral | None | None | None | None | I |
| T/Y | 0.902 | likely_pathogenic | 0.7767 | pathogenic | -0.698 | Destabilizing | 0.998 | D | 0.62 | 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.