Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35198 | 105817;105818;105819 | chr2:178531023;178531022;178531021 | chr2:179395750;179395749;179395748 |
| N2AB | 33557 | 100894;100895;100896 | chr2:178531023;178531022;178531021 | chr2:179395750;179395749;179395748 |
| N2A | 32630 | 98113;98114;98115 | chr2:178531023;178531022;178531021 | chr2:179395750;179395749;179395748 |
| N2B | 26133 | 78622;78623;78624 | chr2:178531023;178531022;178531021 | chr2:179395750;179395749;179395748 |
| Novex-1 | 26258 | 78997;78998;78999 | chr2:178531023;178531022;178531021 | chr2:179395750;179395749;179395748 |
| Novex-2 | 26325 | 79198;79199;79200 | chr2:178531023;178531022;178531021 | chr2:179395750;179395749;179395748 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | rs1363509929  |
-1.386 | 0.005 | N | 0.407 | 0.121 | 0.20549828249 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| N/D | rs1363509929 |
-1.386 | 0.005 | N | 0.407 | 0.121 | 0.20549828249 | gnomAD-4.0.0 | 1.59089E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85749E-06 | 0 | 0 |
| N/K | rs1165290743 |
0.035 | 0.005 | N | 0.383 | 0.119 | 0.126345400529 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.56E-05 | None | 0 | None | 0 | 0 | 0 |
| N/K | rs1165290743 |
0.035 | 0.005 | N | 0.383 | 0.119 | 0.126345400529 | gnomAD-4.0.0 | 6.84141E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51889E-05 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | None | None | None | N | 0.141 | 0.138 | 0.0401082797425 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.17 | likely_benign | 0.1597 | benign | -0.87 | Destabilizing | 0.003 | N | 0.33 | neutral | None | None | None | None | N |
| N/C | 0.2738 | likely_benign | 0.2698 | benign | 0.046 | Stabilizing | 0.448 | N | 0.525 | neutral | None | None | None | None | N |
| N/D | 0.1234 | likely_benign | 0.1165 | benign | -0.11 | Destabilizing | 0.005 | N | 0.407 | neutral | N | 0.488401903 | None | None | N |
| N/E | 0.2841 | likely_benign | 0.2651 | benign | -0.041 | Destabilizing | 0.006 | N | 0.385 | neutral | None | None | None | None | N |
| N/F | 0.399 | ambiguous | 0.3713 | ambiguous | -0.745 | Destabilizing | 0.096 | N | 0.565 | neutral | None | None | None | None | N |
| N/G | 0.2571 | likely_benign | 0.2485 | benign | -1.177 | Destabilizing | 0.003 | N | 0.291 | neutral | None | None | None | None | N |
| N/H | 0.1026 | likely_benign | 0.0973 | benign | -0.914 | Destabilizing | None | N | 0.277 | neutral | N | 0.499504331 | None | None | N |
| N/I | 0.1301 | likely_benign | 0.1178 | benign | -0.102 | Destabilizing | 0.011 | N | 0.549 | neutral | N | 0.462639454 | None | None | N |
| N/K | 0.2102 | likely_benign | 0.1744 | benign | -0.148 | Destabilizing | 0.005 | N | 0.383 | neutral | N | 0.468543919 | None | None | N |
| N/L | 0.1815 | likely_benign | 0.164 | benign | -0.102 | Destabilizing | 0.006 | N | 0.462 | neutral | None | None | None | None | N |
| N/M | 0.2637 | likely_benign | 0.2491 | benign | 0.278 | Stabilizing | 0.177 | N | 0.534 | neutral | None | None | None | None | N |
| N/P | 0.4475 | ambiguous | 0.4051 | ambiguous | -0.329 | Destabilizing | 0.029 | N | 0.542 | neutral | None | None | None | None | N |
| N/Q | 0.2607 | likely_benign | 0.2327 | benign | -0.666 | Destabilizing | 0.029 | N | 0.428 | neutral | None | None | None | None | N |
| N/R | 0.2299 | likely_benign | 0.2023 | benign | -0.16 | Destabilizing | 0.029 | N | 0.371 | neutral | None | None | None | None | N |
| N/S | 0.0675 | likely_benign | 0.067 | benign | -0.707 | Destabilizing | None | N | 0.141 | neutral | N | 0.41956068 | None | None | N |
| N/T | 0.0901 | likely_benign | 0.0857 | benign | -0.443 | Destabilizing | None | N | 0.138 | neutral | N | 0.446131206 | None | None | N |
| N/V | 0.1626 | likely_benign | 0.1474 | benign | -0.329 | Destabilizing | 0.015 | N | 0.479 | neutral | None | None | None | None | N |
| N/W | 0.675 | likely_pathogenic | 0.6703 | pathogenic | -0.509 | Destabilizing | 0.712 | D | 0.547 | neutral | None | None | None | None | N |
| N/Y | 0.1594 | likely_benign | 0.1473 | benign | -0.317 | Destabilizing | 0.039 | N | 0.583 | neutral | N | 0.481091928 | 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.