Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19957 | 60094;60095;60096 | chr2:178592035;178592034;178592033 | chr2:179456762;179456761;179456760 |
| N2AB | 18316 | 55171;55172;55173 | chr2:178592035;178592034;178592033 | chr2:179456762;179456761;179456760 |
| N2A | 17389 | 52390;52391;52392 | chr2:178592035;178592034;178592033 | chr2:179456762;179456761;179456760 |
| N2B | 10892 | 32899;32900;32901 | chr2:178592035;178592034;178592033 | chr2:179456762;179456761;179456760 |
| Novex-1 | 11017 | 33274;33275;33276 | chr2:178592035;178592034;178592033 | chr2:179456762;179456761;179456760 |
| Novex-2 | 11084 | 33475;33476;33477 | chr2:178592035;178592034;178592033 | chr2:179456762;179456761;179456760 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/F | None | None | 0.046 | N | 0.309 | 0.148 | 0.309530620856 | gnomAD-4.0.0 | 5.476E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.19718E-06 | 0 | 0 |
| Y/H | rs772991524  |
0.351 | 0.997 | N | 0.595 | 0.383 | 0.319686207203 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 0 | 0 |
| Y/H | rs772991524 |
0.351 | 0.997 | N | 0.595 | 0.383 | 0.319686207203 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07211E-04 | 0 |
| Y/H | rs772991524 |
0.351 | 0.997 | N | 0.595 | 0.383 | 0.319686207203 | gnomAD-4.0.0 | 1.53868E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39453E-06 | 1.47469E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9156 | likely_pathogenic | 0.8864 | pathogenic | -0.685 | Destabilizing | 0.976 | D | 0.623 | neutral | None | None | None | None | I |
| Y/C | 0.4536 | ambiguous | 0.4042 | ambiguous | 0.136 | Stabilizing | 0.999 | D | 0.735 | prob.delet. | N | 0.463935028 | None | None | I |
| Y/D | 0.8897 | likely_pathogenic | 0.8761 | pathogenic | 0.827 | Stabilizing | 0.997 | D | 0.701 | prob.neutral | N | 0.517958727 | None | None | I |
| Y/E | 0.9532 | likely_pathogenic | 0.9468 | pathogenic | 0.802 | Stabilizing | 0.998 | D | 0.697 | prob.neutral | None | None | None | None | I |
| Y/F | 0.0985 | likely_benign | 0.1039 | benign | -0.388 | Destabilizing | 0.046 | N | 0.309 | neutral | N | 0.402886569 | None | None | I |
| Y/G | 0.9126 | likely_pathogenic | 0.8863 | pathogenic | -0.869 | Destabilizing | 0.993 | D | 0.679 | prob.neutral | None | None | None | None | I |
| Y/H | 0.5117 | ambiguous | 0.4792 | ambiguous | 0.224 | Stabilizing | 0.997 | D | 0.595 | neutral | N | 0.494313863 | None | None | I |
| Y/I | 0.7617 | likely_pathogenic | 0.7513 | pathogenic | -0.229 | Destabilizing | 0.973 | D | 0.623 | neutral | None | None | None | None | I |
| Y/K | 0.9595 | likely_pathogenic | 0.9454 | pathogenic | 0.218 | Stabilizing | 0.998 | D | 0.694 | prob.neutral | None | None | None | None | I |
| Y/L | 0.7874 | likely_pathogenic | 0.7632 | pathogenic | -0.229 | Destabilizing | 0.91 | D | 0.623 | neutral | None | None | None | None | I |
| Y/M | 0.8545 | likely_pathogenic | 0.8381 | pathogenic | -0.066 | Destabilizing | 0.998 | D | 0.637 | neutral | None | None | None | None | I |
| Y/N | 0.6586 | likely_pathogenic | 0.6394 | pathogenic | 0.034 | Stabilizing | 0.997 | D | 0.703 | prob.neutral | N | 0.476381463 | None | None | I |
| Y/P | 0.9932 | likely_pathogenic | 0.9914 | pathogenic | -0.361 | Destabilizing | 0.998 | D | 0.714 | prob.delet. | None | None | None | None | I |
| Y/Q | 0.9201 | likely_pathogenic | 0.9007 | pathogenic | 0.055 | Stabilizing | 0.998 | D | 0.655 | neutral | None | None | None | None | I |
| Y/R | 0.9146 | likely_pathogenic | 0.8902 | pathogenic | 0.509 | Stabilizing | 0.998 | D | 0.704 | prob.neutral | None | None | None | None | I |
| Y/S | 0.8385 | likely_pathogenic | 0.7976 | pathogenic | -0.386 | Destabilizing | 0.991 | D | 0.676 | prob.neutral | N | 0.479864485 | None | None | I |
| Y/T | 0.9328 | likely_pathogenic | 0.9147 | pathogenic | -0.32 | Destabilizing | 0.993 | D | 0.683 | prob.neutral | None | None | None | None | I |
| Y/V | 0.704 | likely_pathogenic | 0.6645 | pathogenic | -0.361 | Destabilizing | 0.953 | D | 0.657 | neutral | None | None | None | None | I |
| Y/W | 0.5517 | ambiguous | 0.5467 | ambiguous | -0.512 | Destabilizing | 0.999 | D | 0.589 | 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.