Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21910 | 65953;65954;65955 | chr2:178583075;178583074;178583073 | chr2:179447802;179447801;179447800 |
| N2AB | 20269 | 61030;61031;61032 | chr2:178583075;178583074;178583073 | chr2:179447802;179447801;179447800 |
| N2A | 19342 | 58249;58250;58251 | chr2:178583075;178583074;178583073 | chr2:179447802;179447801;179447800 |
| N2B | 12845 | 38758;38759;38760 | chr2:178583075;178583074;178583073 | chr2:179447802;179447801;179447800 |
| Novex-1 | 12970 | 39133;39134;39135 | chr2:178583075;178583074;178583073 | chr2:179447802;179447801;179447800 |
| Novex-2 | 13037 | 39334;39335;39336 | chr2:178583075;178583074;178583073 | chr2:179447802;179447801;179447800 |
| 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 | rs749668988  |
None | None | N | 0.093 | 0.126 | 0.608671624233 | 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 |
| I/R | None | None | 0.002 | N | 0.345 | 0.427 | 0.73443042151 | gnomAD-4.0.0 | 6.85237E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65953E-05 |
| I/T | rs146941600 |
-2.579 | 0.007 | N | 0.237 | 0.169 | None | gnomAD-2.1.1 | 1.91954E-04 | None | None | None | None | N | None | 8.36E-05 | 8.59E-05 | None | 0 | 2.16564E-03 | None | 6.59E-05 | None | 0 | 0 | 7.12454E-04 |
| I/T | rs146941600 |
-2.579 | 0.007 | N | 0.237 | 0.169 | None | gnomAD-3.1.2 | 2.82872E-04 | None | None | None | None | N | None | 4.83E-05 | 1.63827E-03 | 0 | 0 | 1.93874E-03 | None | 0 | 0 | 1.47E-05 | 0 | 2.39693E-03 |
| I/T | rs146941600 |
-2.579 | 0.007 | N | 0.237 | 0.169 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| I/T | rs146941600 |
-2.579 | 0.007 | N | 0.237 | 0.169 | None | gnomAD-4.0.0 | 1.50173E-04 | None | None | None | None | N | None | 4.00224E-05 | 4.68353E-04 | None | 0 | 1.12349E-03 | None | 0 | 0 | 6.78774E-06 | 1.10069E-05 | 2.43722E-03 |
| I/V | rs749668988 |
-1.471 | 0.001 | N | 0.149 | 0.091 | 0.436671004673 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.07E-06 | 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 | 0.4764 | ambiguous | 0.4434 | ambiguous | -2.102 | Highly Destabilizing | 0.129 | N | 0.327 | neutral | None | None | None | None | N |
| I/C | 0.5548 | ambiguous | 0.5276 | ambiguous | -1.198 | Destabilizing | 0.94 | D | 0.515 | neutral | None | None | None | None | N |
| I/D | 0.8031 | likely_pathogenic | 0.7788 | pathogenic | -1.794 | Destabilizing | 0.716 | D | 0.571 | neutral | None | None | None | None | N |
| I/E | 0.5969 | likely_pathogenic | 0.5886 | pathogenic | -1.69 | Destabilizing | 0.418 | N | 0.541 | neutral | None | None | None | None | N |
| I/F | 0.1382 | likely_benign | 0.1306 | benign | -1.32 | Destabilizing | 0.264 | N | 0.483 | neutral | None | None | None | None | N |
| I/G | 0.7185 | likely_pathogenic | 0.6749 | pathogenic | -2.535 | Highly Destabilizing | 0.418 | N | 0.52 | neutral | None | None | None | None | N |
| I/H | 0.5002 | ambiguous | 0.4707 | ambiguous | -1.825 | Destabilizing | 0.983 | D | 0.538 | neutral | None | None | None | None | N |
| I/K | 0.3348 | likely_benign | 0.3314 | benign | -1.613 | Destabilizing | 0.213 | N | 0.502 | neutral | N | 0.50035248 | None | None | N |
| I/L | 0.1214 | likely_benign | 0.1119 | benign | -0.92 | Destabilizing | None | N | 0.093 | neutral | N | 0.443245616 | None | None | N |
| I/M | 0.1002 | likely_benign | 0.0932 | benign | -0.66 | Destabilizing | 0.021 | N | 0.191 | neutral | N | 0.465354472 | None | None | N |
| I/N | 0.3615 | ambiguous | 0.3357 | benign | -1.571 | Destabilizing | 0.716 | D | 0.573 | neutral | None | None | None | None | N |
| I/P | 0.9237 | likely_pathogenic | 0.905 | pathogenic | -1.287 | Destabilizing | 0.836 | D | 0.576 | neutral | None | None | None | None | N |
| I/Q | 0.3799 | ambiguous | 0.3644 | ambiguous | -1.61 | Destabilizing | 0.716 | D | 0.576 | neutral | None | None | None | None | N |
| I/R | 0.2786 | likely_benign | 0.2684 | benign | -1.118 | Destabilizing | 0.002 | N | 0.345 | neutral | N | 0.478091696 | None | None | N |
| I/S | 0.4001 | ambiguous | 0.3701 | ambiguous | -2.228 | Highly Destabilizing | 0.264 | N | 0.465 | neutral | None | None | None | None | N |
| I/T | 0.3273 | likely_benign | 0.3138 | benign | -1.996 | Destabilizing | 0.007 | N | 0.237 | neutral | N | 0.471107008 | None | None | N |
| I/V | 0.088 | likely_benign | 0.0851 | benign | -1.287 | Destabilizing | 0.001 | N | 0.149 | neutral | N | 0.4385118 | None | None | N |
| I/W | 0.6491 | likely_pathogenic | 0.6297 | pathogenic | -1.55 | Destabilizing | 0.983 | D | 0.561 | neutral | None | None | None | None | N |
| I/Y | 0.3797 | ambiguous | 0.3565 | ambiguous | -1.301 | Destabilizing | 0.836 | D | 0.533 | 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.