Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29658 | 89197;89198;89199 | chr2:178554139;178554138;178554137 | chr2:179418866;179418865;179418864 |
| N2AB | 28017 | 84274;84275;84276 | chr2:178554139;178554138;178554137 | chr2:179418866;179418865;179418864 |
| N2A | 27090 | 81493;81494;81495 | chr2:178554139;178554138;178554137 | chr2:179418866;179418865;179418864 |
| N2B | 20593 | 62002;62003;62004 | chr2:178554139;178554138;178554137 | chr2:179418866;179418865;179418864 |
| Novex-1 | 20718 | 62377;62378;62379 | chr2:178554139;178554138;178554137 | chr2:179418866;179418865;179418864 |
| Novex-2 | 20785 | 62578;62579;62580 | chr2:178554139;178554138;178554137 | chr2:179418866;179418865;179418864 |
| 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/T | rs750026544  |
-0.169 | None | N | 0.113 | 0.059 | 0.162503812791 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 5.57E-05 | None | 9.81E-05 | None | 0 | 8.97E-06 | 0 |
| I/T | rs750026544 |
-0.169 | None | N | 0.113 | 0.059 | 0.162503812791 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07039E-04 | 0 |
| I/T | rs750026544 |
-0.169 | None | N | 0.113 | 0.059 | 0.162503812791 | gnomAD-4.0.0 | 9.91508E-06 | None | None | None | None | I | None | 1.33494E-05 | 1.66678E-05 | None | 0 | 2.22846E-05 | None | 0 | 0 | 5.93326E-06 | 6.58762E-05 | 0 |
| I/V | rs200193877 |
-0.048 | None | N | 0.061 | 0.094 | None | gnomAD-2.1.1 | 1.64902E-04 | None | None | None | None | I | None | 4.13E-05 | 5.66E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.30896E-04 | 1.40924E-04 |
| I/V | rs200193877 |
-0.048 | None | N | 0.061 | 0.094 | None | gnomAD-3.1.2 | 2.36531E-04 | None | None | None | None | I | None | 2.41E-05 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 4.9978E-04 | 0 | 0 |
| I/V | rs200193877 |
-0.048 | None | N | 0.061 | 0.094 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| I/V | rs200193877 |
-0.048 | None | N | 0.061 | 0.094 | None | gnomAD-4.0.0 | 4.58525E-04 | None | None | None | None | I | None | 6.66187E-05 | 4.99817E-05 | None | 0 | 2.22916E-05 | None | 0 | 0 | 5.68734E-04 | 1.09798E-05 | 9.44242E-04 |
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 | 0.0664 | likely_benign | 0.068 | benign | -0.435 | Destabilizing | None | N | 0.108 | neutral | None | None | None | None | I |
| I/C | 0.3437 | ambiguous | 0.3916 | ambiguous | -0.798 | Destabilizing | 0.245 | N | 0.278 | neutral | None | None | None | None | I |
| I/D | 0.1927 | likely_benign | 0.2012 | benign | -0.255 | Destabilizing | 0.018 | N | 0.293 | neutral | None | None | None | None | I |
| I/E | 0.147 | likely_benign | 0.152 | benign | -0.356 | Destabilizing | 0.018 | N | 0.295 | neutral | None | None | None | None | I |
| I/F | 0.1042 | likely_benign | 0.1184 | benign | -0.646 | Destabilizing | 0.033 | N | 0.342 | neutral | N | 0.479960486 | None | None | I |
| I/G | 0.157 | likely_benign | 0.1857 | benign | -0.52 | Destabilizing | 0.004 | N | 0.281 | neutral | None | None | None | None | I |
| I/H | 0.1956 | likely_benign | 0.2187 | benign | 0.065 | Stabilizing | 0.497 | N | 0.345 | neutral | None | None | None | None | I |
| I/K | 0.136 | likely_benign | 0.134 | benign | -0.331 | Destabilizing | 0.018 | N | 0.295 | neutral | None | None | None | None | I |
| I/L | 0.0678 | likely_benign | 0.0696 | benign | -0.337 | Destabilizing | 0.001 | N | 0.121 | neutral | N | 0.41352485 | None | None | I |
| I/M | 0.0643 | likely_benign | 0.0668 | benign | -0.593 | Destabilizing | 0.108 | N | 0.317 | neutral | N | 0.477325613 | None | None | I |
| I/N | 0.0889 | likely_benign | 0.0892 | benign | -0.191 | Destabilizing | 0.014 | N | 0.324 | neutral | N | 0.457603701 | None | None | I |
| I/P | 0.1556 | likely_benign | 0.1713 | benign | -0.342 | Destabilizing | 0.037 | N | 0.368 | neutral | None | None | None | None | I |
| I/Q | 0.1357 | likely_benign | 0.1452 | benign | -0.381 | Destabilizing | 0.085 | N | 0.503 | neutral | None | None | None | None | I |
| I/R | 0.1276 | likely_benign | 0.1312 | benign | 0.128 | Stabilizing | 0.044 | N | 0.443 | neutral | None | None | None | None | I |
| I/S | 0.0766 | likely_benign | 0.0771 | benign | -0.557 | Destabilizing | None | N | 0.117 | neutral | N | 0.410945905 | None | None | I |
| I/T | 0.0598 | likely_benign | 0.0596 | benign | -0.561 | Destabilizing | None | N | 0.113 | neutral | N | 0.407809599 | None | None | I |
| I/V | 0.0512 | likely_benign | 0.0508 | benign | -0.342 | Destabilizing | None | N | 0.061 | neutral | N | 0.432630686 | None | None | I |
| I/W | 0.5487 | ambiguous | 0.6242 | pathogenic | -0.664 | Destabilizing | 0.788 | D | 0.294 | neutral | None | None | None | None | I |
| I/Y | 0.3003 | likely_benign | 0.3378 | benign | -0.428 | Destabilizing | 0.085 | N | 0.423 | 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.