Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24311 | 73156;73157;73158 | chr2:178573201;178573200;178573199 | chr2:179437928;179437927;179437926 |
| N2AB | 22670 | 68233;68234;68235 | chr2:178573201;178573200;178573199 | chr2:179437928;179437927;179437926 |
| N2A | 21743 | 65452;65453;65454 | chr2:178573201;178573200;178573199 | chr2:179437928;179437927;179437926 |
| N2B | 15246 | 45961;45962;45963 | chr2:178573201;178573200;178573199 | chr2:179437928;179437927;179437926 |
| Novex-1 | 15371 | 46336;46337;46338 | chr2:178573201;178573200;178573199 | chr2:179437928;179437927;179437926 |
| Novex-2 | 15438 | 46537;46538;46539 | chr2:178573201;178573200;178573199 | chr2:179437928;179437927;179437926 |
| 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/A | rs56201325  |
-1.171 | None | N | 0.167 | 0.054 | None | gnomAD-2.1.1 | 4.04628E-03 | None | None | None | None | N | None | 7.86164E-04 | 1.17069E-03 | None | 0 | 0 | None | 1.69022E-04 | None | 8.49455E-03 | 6.39959E-03 | 5.01145E-03 |
| T/A | rs56201325 |
-1.171 | None | N | 0.167 | 0.054 | None | gnomAD-3.1.2 | 3.44479E-03 | None | None | None | None | N | None | 7.72164E-04 | 1.44149E-03 | 0 | 0 | 0 | None | 7.34187E-03 | 0 | 5.66193E-03 | 0 | 3.34608E-03 |
| T/A | rs56201325 |
-1.171 | None | N | 0.167 | 0.054 | None | 1000 genomes | 7.98722E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 3E-03 | None | None | None | 0 | None |
| T/A | rs56201325 |
-1.171 | None | N | 0.167 | 0.054 | None | gnomAD-4.0.0 | 4.24777E-03 | None | None | None | None | N | None | 8.13919E-04 | 1.27282E-03 | None | 0 | 0 | None | 8.43128E-03 | 4.97678E-04 | 5.01925E-03 | 1.21905E-04 | 3.82342E-03 |
| T/N | None | None | 0.001 | N | 0.18 | 0.145 | 0.258779203287 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| T/P | None | None | 0.475 | N | 0.579 | 0.099 | 0.151104730317 | gnomAD-4.0.0 | 6.86634E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.74398E-04 | 0 | 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 | 0.0524 | likely_benign | 0.0507 | benign | -1.064 | Destabilizing | None | N | 0.167 | neutral | N | 0.389183766 | None | None | N |
| T/C | 0.2188 | likely_benign | 0.2052 | benign | -0.625 | Destabilizing | 0.002 | N | 0.321 | neutral | None | None | None | None | N |
| T/D | 0.3681 | ambiguous | 0.3051 | benign | -0.461 | Destabilizing | 0.109 | N | 0.415 | neutral | None | None | None | None | N |
| T/E | 0.2949 | likely_benign | 0.2466 | benign | -0.427 | Destabilizing | 0.196 | N | 0.409 | neutral | None | None | None | None | N |
| T/F | 0.199 | likely_benign | 0.183 | benign | -0.968 | Destabilizing | 0.808 | D | 0.679 | prob.neutral | None | None | None | None | N |
| T/G | 0.1547 | likely_benign | 0.1431 | benign | -1.361 | Destabilizing | 0.109 | N | 0.437 | neutral | None | None | None | None | N |
| T/H | 0.2558 | likely_benign | 0.2283 | benign | -1.57 | Destabilizing | 0.808 | D | 0.581 | neutral | None | None | None | None | N |
| T/I | 0.094 | likely_benign | 0.093 | benign | -0.346 | Destabilizing | 0.085 | N | 0.456 | neutral | N | 0.439111154 | None | None | N |
| T/K | 0.2464 | likely_benign | 0.2133 | benign | -0.909 | Destabilizing | 0.196 | N | 0.407 | neutral | None | None | None | None | N |
| T/L | 0.0754 | likely_benign | 0.0729 | benign | -0.346 | Destabilizing | 0.109 | N | 0.41 | neutral | None | None | None | None | N |
| T/M | 0.0853 | likely_benign | 0.0855 | benign | -0.059 | Destabilizing | 0.808 | D | 0.432 | neutral | None | None | None | None | N |
| T/N | 0.1188 | likely_benign | 0.1028 | benign | -0.905 | Destabilizing | 0.001 | N | 0.18 | neutral | N | 0.452792527 | None | None | N |
| T/P | 0.0596 | likely_benign | 0.0557 | benign | -0.553 | Destabilizing | 0.475 | N | 0.579 | neutral | N | 0.336445359 | None | None | N |
| T/Q | 0.2207 | likely_benign | 0.2002 | benign | -1.014 | Destabilizing | 0.546 | D | 0.592 | neutral | None | None | None | None | N |
| T/R | 0.2215 | likely_benign | 0.1925 | benign | -0.706 | Destabilizing | 0.372 | N | 0.589 | neutral | None | None | None | None | N |
| T/S | 0.0811 | likely_benign | 0.0771 | benign | -1.2 | Destabilizing | 0.002 | N | 0.155 | neutral | N | 0.380372282 | None | None | N |
| T/V | 0.0746 | likely_benign | 0.0753 | benign | -0.553 | Destabilizing | 0.001 | N | 0.21 | neutral | None | None | None | None | N |
| T/W | 0.6028 | likely_pathogenic | 0.5791 | pathogenic | -0.894 | Destabilizing | 0.98 | D | 0.683 | prob.neutral | None | None | None | None | N |
| T/Y | 0.2709 | likely_benign | 0.2454 | benign | -0.686 | Destabilizing | 0.928 | D | 0.665 | prob.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.