Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28187 | 84784;84785;84786 | chr2:178561573;178561572;178561571 | chr2:179426300;179426299;179426298 |
| N2AB | 26546 | 79861;79862;79863 | chr2:178561573;178561572;178561571 | chr2:179426300;179426299;179426298 |
| N2A | 25619 | 77080;77081;77082 | chr2:178561573;178561572;178561571 | chr2:179426300;179426299;179426298 |
| N2B | 19122 | 57589;57590;57591 | chr2:178561573;178561572;178561571 | chr2:179426300;179426299;179426298 |
| Novex-1 | 19247 | 57964;57965;57966 | chr2:178561573;178561572;178561571 | chr2:179426300;179426299;179426298 |
| Novex-2 | 19314 | 58165;58166;58167 | chr2:178561573;178561572;178561571 | chr2:179426300;179426299;179426298 |
| 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 | rs1221889321  |
-0.865 | None | N | 0.146 | 0.079 | 0.315903272564 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| I/T | rs1221889321 |
-0.865 | None | N | 0.146 | 0.079 | 0.315903272564 | gnomAD-4.0.0 | 1.59257E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86007E-06 | 0 | 0 |
| I/V | rs2154159829 |
None | 0.001 | N | 0.087 | 0.035 | 0.313210971179 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.92901E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs2154159829 |
None | 0.001 | N | 0.087 | 0.035 | 0.313210971179 | gnomAD-4.0.0 | 2.0296E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.27221E-04 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1451 | likely_benign | 0.151 | benign | -0.874 | Destabilizing | 0.035 | N | 0.427 | neutral | None | None | None | None | I |
| I/C | 0.6067 | likely_pathogenic | 0.5923 | pathogenic | -0.682 | Destabilizing | 0.935 | D | 0.373 | neutral | None | None | None | None | I |
| I/D | 0.6979 | likely_pathogenic | 0.6911 | pathogenic | -0.361 | Destabilizing | 0.38 | N | 0.402 | neutral | None | None | None | None | I |
| I/E | 0.5345 | ambiguous | 0.5483 | ambiguous | -0.44 | Destabilizing | 0.38 | N | 0.411 | neutral | None | None | None | None | I |
| I/F | 0.1387 | likely_benign | 0.1425 | benign | -0.759 | Destabilizing | 0.188 | N | 0.384 | neutral | N | 0.48444661 | None | None | I |
| I/G | 0.5082 | ambiguous | 0.505 | ambiguous | -1.075 | Destabilizing | 0.149 | N | 0.4 | neutral | None | None | None | None | I |
| I/H | 0.4176 | ambiguous | 0.407 | ambiguous | -0.279 | Destabilizing | 0.935 | D | 0.351 | neutral | None | None | None | None | I |
| I/K | 0.3192 | likely_benign | 0.3103 | benign | -0.54 | Destabilizing | 0.149 | N | 0.421 | neutral | None | None | None | None | I |
| I/L | 0.0588 | likely_benign | 0.0668 | benign | -0.456 | Destabilizing | None | N | 0.073 | neutral | N | 0.436073636 | None | None | I |
| I/M | 0.0761 | likely_benign | 0.0803 | benign | -0.434 | Destabilizing | 0.188 | N | 0.405 | neutral | N | 0.468570854 | None | None | I |
| I/N | 0.2585 | likely_benign | 0.2498 | benign | -0.314 | Destabilizing | 0.317 | N | 0.402 | neutral | N | 0.46969649 | None | None | I |
| I/P | 0.8148 | likely_pathogenic | 0.8083 | pathogenic | -0.561 | Destabilizing | 0.555 | D | 0.412 | neutral | None | None | None | None | I |
| I/Q | 0.3398 | likely_benign | 0.3376 | benign | -0.552 | Destabilizing | 0.555 | D | 0.389 | neutral | None | None | None | None | I |
| I/R | 0.2138 | likely_benign | 0.204 | benign | 0.075 | Stabilizing | 0.38 | N | 0.406 | neutral | None | None | None | None | I |
| I/S | 0.1802 | likely_benign | 0.1773 | benign | -0.807 | Destabilizing | 0.062 | N | 0.347 | neutral | N | 0.4957753 | None | None | I |
| I/T | 0.0592 | likely_benign | 0.0633 | benign | -0.775 | Destabilizing | None | N | 0.146 | neutral | N | 0.411001833 | None | None | I |
| I/V | 0.0754 | likely_benign | 0.0772 | benign | -0.561 | Destabilizing | 0.001 | N | 0.087 | neutral | N | 0.500527759 | None | None | I |
| I/W | 0.6898 | likely_pathogenic | 0.6918 | pathogenic | -0.759 | Destabilizing | 0.935 | D | 0.403 | neutral | None | None | None | None | I |
| I/Y | 0.4936 | ambiguous | 0.4944 | ambiguous | -0.528 | Destabilizing | 0.555 | D | 0.398 | 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.