Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15250 | 45973;45974;45975 | chr2:178620862;178620861;178620860 | chr2:179485589;179485588;179485587 |
| N2AB | 13609 | 41050;41051;41052 | chr2:178620862;178620861;178620860 | chr2:179485589;179485588;179485587 |
| N2A | 12682 | 38269;38270;38271 | chr2:178620862;178620861;178620860 | chr2:179485589;179485588;179485587 |
| N2B | 6185 | 18778;18779;18780 | chr2:178620862;178620861;178620860 | chr2:179485589;179485588;179485587 |
| Novex-1 | 6310 | 19153;19154;19155 | chr2:178620862;178620861;178620860 | chr2:179485589;179485588;179485587 |
| Novex-2 | 6377 | 19354;19355;19356 | chr2:178620862;178620861;178620860 | chr2:179485589;179485588;179485587 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs776190494  |
-0.265 | 1.0 | D | 0.543 | 0.472 | 0.444305618086 | gnomAD-2.1.1 | 8.08E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54065E-04 | None | 0 | 0 | 0 |
| S/C | rs776190494 |
-0.265 | 1.0 | D | 0.543 | 0.472 | 0.444305618086 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.14079E-04 | 0 |
| S/C | rs776190494 |
-0.265 | 1.0 | D | 0.543 | 0.472 | 0.444305618086 | gnomAD-4.0.0 | 4.03089E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.91943E-04 | 3.20523E-05 |
| S/G | None | None | 0.104 | N | 0.275 | 0.15 | 0.187945064343 | gnomAD-4.0.0 | 6.84641E-07 | None | None | None | None | N | None | 0 | 2.23994E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | None | None | 0.994 | N | 0.449 | 0.237 | 0.276898752692 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2485 | likely_benign | 0.2406 | benign | -0.545 | Destabilizing | 0.98 | D | 0.408 | neutral | None | None | None | None | N |
| S/C | 0.3154 | likely_benign | 0.2881 | benign | -0.376 | Destabilizing | 1.0 | D | 0.543 | neutral | D | 0.608902738 | None | None | N |
| S/D | 0.7125 | likely_pathogenic | 0.6542 | pathogenic | 0.532 | Stabilizing | 0.996 | D | 0.461 | neutral | None | None | None | None | N |
| S/E | 0.9356 | likely_pathogenic | 0.9102 | pathogenic | 0.47 | Stabilizing | 0.999 | D | 0.459 | neutral | None | None | None | None | N |
| S/F | 0.7507 | likely_pathogenic | 0.7145 | pathogenic | -1.076 | Destabilizing | 1.0 | D | 0.576 | neutral | None | None | None | None | N |
| S/G | 0.17 | likely_benign | 0.1868 | benign | -0.686 | Destabilizing | 0.104 | N | 0.275 | neutral | N | 0.440351496 | None | None | N |
| S/H | 0.744 | likely_pathogenic | 0.7123 | pathogenic | -1.088 | Destabilizing | 1.0 | D | 0.539 | neutral | None | None | None | None | N |
| S/I | 0.7655 | likely_pathogenic | 0.7076 | pathogenic | -0.297 | Destabilizing | 0.999 | D | 0.569 | neutral | D | 0.607644474 | None | None | N |
| S/K | 0.9643 | likely_pathogenic | 0.9541 | pathogenic | -0.361 | Destabilizing | 0.996 | D | 0.488 | neutral | None | None | None | None | N |
| S/L | 0.4537 | ambiguous | 0.4084 | ambiguous | -0.297 | Destabilizing | 1.0 | D | 0.531 | neutral | None | None | None | None | N |
| S/M | 0.6977 | likely_pathogenic | 0.6612 | pathogenic | -0.166 | Destabilizing | 1.0 | D | 0.543 | neutral | None | None | None | None | N |
| S/N | 0.3322 | likely_benign | 0.3133 | benign | -0.197 | Destabilizing | 0.994 | D | 0.486 | neutral | N | 0.444653549 | None | None | N |
| S/P | 0.9437 | likely_pathogenic | 0.9241 | pathogenic | -0.35 | Destabilizing | 1.0 | D | 0.535 | neutral | None | None | None | None | N |
| S/Q | 0.9077 | likely_pathogenic | 0.8871 | pathogenic | -0.349 | Destabilizing | 1.0 | D | 0.521 | neutral | None | None | None | None | N |
| S/R | 0.9387 | likely_pathogenic | 0.9231 | pathogenic | -0.235 | Destabilizing | 0.999 | D | 0.535 | neutral | D | 0.565988104 | None | None | N |
| S/T | 0.1631 | likely_benign | 0.1498 | benign | -0.322 | Destabilizing | 0.994 | D | 0.449 | neutral | N | 0.45906353 | None | None | N |
| S/V | 0.7375 | likely_pathogenic | 0.6719 | pathogenic | -0.35 | Destabilizing | 1.0 | D | 0.565 | neutral | None | None | None | None | N |
| S/W | 0.8847 | likely_pathogenic | 0.8526 | pathogenic | -1.065 | Destabilizing | 1.0 | D | 0.635 | neutral | None | None | None | None | N |
| S/Y | 0.6671 | likely_pathogenic | 0.6098 | pathogenic | -0.778 | Destabilizing | 1.0 | D | 0.576 | 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.