Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32316 | 97171;97172;97173 | chr2:178542908;178542907;178542906 | chr2:179407635;179407634;179407633 |
| N2AB | 30675 | 92248;92249;92250 | chr2:178542908;178542907;178542906 | chr2:179407635;179407634;179407633 |
| N2A | 29748 | 89467;89468;89469 | chr2:178542908;178542907;178542906 | chr2:179407635;179407634;179407633 |
| N2B | 23251 | 69976;69977;69978 | chr2:178542908;178542907;178542906 | chr2:179407635;179407634;179407633 |
| Novex-1 | 23376 | 70351;70352;70353 | chr2:178542908;178542907;178542906 | chr2:179407635;179407634;179407633 |
| Novex-2 | 23443 | 70552;70553;70554 | chr2:178542908;178542907;178542906 | chr2:179407635;179407634;179407633 |
| 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/S | None | None | 0.101 | N | 0.349 | 0.359 | 0.79540345994 | gnomAD-4.0.0 | 6.84562E-07 | None | None | None | None | I | None | 0 | 2.23644E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1366924258  |
None | 0.183 | N | 0.362 | 0.242 | 0.605748623547 | gnomAD-4.0.0 | 6.84562E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00001E-07 | 0 | 0 |
| I/V | None | None | None | N | 0.119 | 0.068 | 0.464183351471 | gnomAD-4.0.0 | 1.59336E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86402E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5455 | ambiguous | 0.5165 | ambiguous | -2.235 | Highly Destabilizing | 0.004 | N | 0.155 | neutral | None | None | None | None | I |
| I/C | 0.7604 | likely_pathogenic | 0.7382 | pathogenic | -1.302 | Destabilizing | 0.836 | D | 0.409 | neutral | None | None | None | None | I |
| I/D | 0.9496 | likely_pathogenic | 0.9263 | pathogenic | -2.384 | Highly Destabilizing | 0.001 | N | 0.32 | neutral | None | None | None | None | I |
| I/E | 0.8639 | likely_pathogenic | 0.8364 | pathogenic | -2.254 | Highly Destabilizing | 0.264 | N | 0.425 | neutral | None | None | None | None | I |
| I/F | 0.2178 | likely_benign | 0.1852 | benign | -1.438 | Destabilizing | 0.351 | N | 0.42 | neutral | N | 0.514551141 | None | None | I |
| I/G | 0.8874 | likely_pathogenic | 0.86 | pathogenic | -2.675 | Highly Destabilizing | 0.228 | N | 0.387 | neutral | None | None | None | None | I |
| I/H | 0.739 | likely_pathogenic | 0.6929 | pathogenic | -1.974 | Destabilizing | 0.94 | D | 0.456 | neutral | None | None | None | None | I |
| I/K | 0.6942 | likely_pathogenic | 0.6709 | pathogenic | -1.829 | Destabilizing | 0.593 | D | 0.437 | neutral | None | None | None | None | I |
| I/L | 0.1238 | likely_benign | 0.1158 | benign | -1.013 | Destabilizing | 0.047 | N | 0.296 | neutral | N | 0.483572086 | None | None | I |
| I/M | 0.1464 | likely_benign | 0.1428 | benign | -0.712 | Destabilizing | 0.655 | D | 0.422 | neutral | N | 0.487809605 | None | None | I |
| I/N | 0.6881 | likely_pathogenic | 0.6542 | pathogenic | -1.908 | Destabilizing | 0.351 | N | 0.481 | neutral | N | 0.507181307 | None | None | I |
| I/P | 0.9723 | likely_pathogenic | 0.9524 | pathogenic | -1.397 | Destabilizing | 0.593 | D | 0.458 | neutral | None | None | None | None | I |
| I/Q | 0.6971 | likely_pathogenic | 0.6847 | pathogenic | -1.936 | Destabilizing | 0.836 | D | 0.477 | neutral | None | None | None | None | I |
| I/R | 0.5975 | likely_pathogenic | 0.5419 | ambiguous | -1.313 | Destabilizing | 0.836 | D | 0.481 | neutral | None | None | None | None | I |
| I/S | 0.5971 | likely_pathogenic | 0.5616 | ambiguous | -2.496 | Highly Destabilizing | 0.101 | N | 0.349 | neutral | N | 0.506167349 | None | None | I |
| I/T | 0.4484 | ambiguous | 0.4399 | ambiguous | -2.239 | Highly Destabilizing | 0.183 | N | 0.362 | neutral | N | 0.4967921 | None | None | I |
| I/V | 0.0781 | likely_benign | 0.0772 | benign | -1.397 | Destabilizing | None | N | 0.119 | neutral | N | 0.443549474 | None | None | I |
| I/W | 0.8352 | likely_pathogenic | 0.791 | pathogenic | -1.728 | Destabilizing | 0.983 | D | 0.489 | neutral | None | None | None | None | I |
| I/Y | 0.6087 | likely_pathogenic | 0.5358 | ambiguous | -1.456 | Destabilizing | 0.836 | D | 0.421 | 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.