Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30731 | 92416;92417;92418 | chr2:178549435;178549434;178549433 | chr2:179414162;179414161;179414160 |
| N2AB | 29090 | 87493;87494;87495 | chr2:178549435;178549434;178549433 | chr2:179414162;179414161;179414160 |
| N2A | 28163 | 84712;84713;84714 | chr2:178549435;178549434;178549433 | chr2:179414162;179414161;179414160 |
| N2B | 21666 | 65221;65222;65223 | chr2:178549435;178549434;178549433 | chr2:179414162;179414161;179414160 |
| Novex-1 | 21791 | 65596;65597;65598 | chr2:178549435;178549434;178549433 | chr2:179414162;179414161;179414160 |
| Novex-2 | 21858 | 65797;65798;65799 | chr2:178549435;178549434;178549433 | chr2:179414162;179414161;179414160 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs16866391  |
-0.877 | 0.005 | N | 0.216 | 0.104 | 0.0666544352282 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 4.67E-05 | 1.79E-05 | 0 |
| I/L | rs16866391 |
-0.877 | 0.005 | N | 0.216 | 0.104 | 0.0666544352282 | gnomAD-4.0.0 | 3.49651E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87589E-05 | 0 | 4.14604E-05 | 2.32002E-05 | 3.32071E-05 |
| I/V | rs16866391 |
-1.139 | None | N | 0.097 | 0.062 | None | gnomAD-2.1.1 | 3.52571E-02 | None | None | None | None | N | None | 3.26635E-03 | 2.23203E-01 | None | 7.77303E-04 | 6.58827E-02 | None | 4.4868E-03 | None | 2.25044E-03 | 1.72186E-03 | 2.64124E-02 |
| I/V | rs16866391 |
-1.139 | None | N | 0.097 | 0.062 | None | gnomAD-3.1.2 | 1.55402E-02 | None | None | None | None | N | None | 2.94274E-03 | 1.10151E-01 | 0 | 1.44092E-03 | 7.14836E-02 | None | 1.88359E-03 | 3.16456E-03 | 1.4699E-03 | 5.7995E-03 | 1.72084E-02 |
| I/V | rs16866391 |
-1.139 | None | N | 0.097 | 0.062 | None | 1000 genomes | 3.47444E-02 | None | None | None | None | N | None | 8E-04 | 1.614E-01 | None | None | 5.65E-02 | 0 | None | None | None | 4.1E-03 | None |
| I/V | rs16866391 |
-1.139 | None | N | 0.097 | 0.062 | None | gnomAD-4.0.0 | 1.09846E-02 | None | None | None | None | N | None | 2.69686E-03 | 1.84631E-01 | None | 1.15051E-03 | 8.48172E-02 | None | 2.15875E-03 | 1.81999E-03 | 1.16092E-03 | 4.98737E-03 | 1.02018E-02 |
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 | 0.2898 | likely_benign | 0.3489 | ambiguous | -1.564 | Destabilizing | 0.035 | N | 0.263 | neutral | None | None | None | None | N |
| I/C | 0.5168 | ambiguous | 0.5865 | pathogenic | -1.345 | Destabilizing | 0.824 | D | 0.374 | neutral | None | None | None | None | N |
| I/D | 0.719 | likely_pathogenic | 0.7961 | pathogenic | -1.116 | Destabilizing | 0.555 | D | 0.517 | neutral | None | None | None | None | N |
| I/E | 0.5619 | ambiguous | 0.6285 | pathogenic | -1.126 | Destabilizing | 0.555 | D | 0.517 | neutral | None | None | None | None | N |
| I/F | 0.2439 | likely_benign | 0.3218 | benign | -1.41 | Destabilizing | 0.38 | N | 0.397 | neutral | None | None | None | None | N |
| I/G | 0.5637 | ambiguous | 0.6767 | pathogenic | -1.85 | Destabilizing | 0.262 | N | 0.483 | neutral | None | None | None | None | N |
| I/H | 0.58 | likely_pathogenic | 0.6799 | pathogenic | -1.212 | Destabilizing | 0.935 | D | 0.512 | neutral | None | None | None | None | N |
| I/K | 0.4372 | ambiguous | 0.5143 | ambiguous | -0.93 | Destabilizing | 0.484 | N | 0.517 | neutral | N | 0.481323193 | None | None | N |
| I/L | 0.1522 | likely_benign | 0.1849 | benign | -0.859 | Destabilizing | 0.005 | N | 0.216 | neutral | N | 0.51074754 | None | None | N |
| I/M | 0.121 | likely_benign | 0.1434 | benign | -0.752 | Destabilizing | 0.317 | N | 0.423 | neutral | N | 0.503973351 | None | None | N |
| I/N | 0.3164 | likely_benign | 0.3538 | ambiguous | -0.784 | Destabilizing | 0.791 | D | 0.521 | neutral | None | None | None | None | N |
| I/P | 0.6775 | likely_pathogenic | 0.753 | pathogenic | -1.064 | Destabilizing | 0.555 | D | 0.527 | neutral | None | None | None | None | N |
| I/Q | 0.4516 | ambiguous | 0.5293 | ambiguous | -1.012 | Destabilizing | 0.791 | D | 0.528 | neutral | None | None | None | None | N |
| I/R | 0.3458 | ambiguous | 0.4422 | ambiguous | -0.432 | Destabilizing | 0.484 | N | 0.521 | neutral | N | 0.469219645 | None | None | N |
| I/S | 0.2719 | likely_benign | 0.3156 | benign | -1.425 | Destabilizing | 0.149 | N | 0.426 | neutral | None | None | None | None | N |
| I/T | 0.1566 | likely_benign | 0.1841 | benign | -1.317 | Destabilizing | 0.062 | N | 0.386 | neutral | N | 0.480926065 | None | None | N |
| I/V | 0.054 | likely_benign | 0.0573 | benign | -1.064 | Destabilizing | None | N | 0.097 | neutral | N | 0.412524773 | None | None | N |
| I/W | 0.8505 | likely_pathogenic | 0.9168 | pathogenic | -1.446 | Destabilizing | 0.935 | D | 0.582 | neutral | None | None | None | None | N |
| I/Y | 0.5618 | ambiguous | 0.6376 | pathogenic | -1.157 | Destabilizing | 0.555 | D | 0.413 | 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.