Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15260 | 46003;46004;46005 | chr2:178620832;178620831;178620830 | chr2:179485559;179485558;179485557 |
| N2AB | 13619 | 41080;41081;41082 | chr2:178620832;178620831;178620830 | chr2:179485559;179485558;179485557 |
| N2A | 12692 | 38299;38300;38301 | chr2:178620832;178620831;178620830 | chr2:179485559;179485558;179485557 |
| N2B | 6195 | 18808;18809;18810 | chr2:178620832;178620831;178620830 | chr2:179485559;179485558;179485557 |
| Novex-1 | 6320 | 19183;19184;19185 | chr2:178620832;178620831;178620830 | chr2:179485559;179485558;179485557 |
| Novex-2 | 6387 | 19384;19385;19386 | chr2:178620832;178620831;178620830 | chr2:179485559;179485558;179485557 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | rs552053581  |
-1.001 | 0.966 | N | 0.575 | 0.373 | 0.771099386941 | gnomAD-2.1.1 | 4.88581E-04 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 3.85823E-03 | None | 0 | 0 | 3.32447E-04 |
| L/P | rs552053581 |
-1.001 | 0.966 | N | 0.575 | 0.373 | 0.771099386941 | gnomAD-3.1.2 | 1.05485E-04 | None | None | None | None | N | None | 2.42E-05 | 1.97213E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.49584E-03 | 0 |
| L/P | rs552053581 |
-1.001 | 0.966 | N | 0.575 | 0.373 | 0.771099386941 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| L/P | rs552053581 |
-1.001 | 0.966 | N | 0.575 | 0.373 | 0.771099386941 | gnomAD-4.0.0 | 2.41241E-04 | None | None | None | None | N | None | 1.33618E-05 | 6.67802E-05 | None | 0 | 0 | None | 0 | 0 | 1.69621E-06 | 3.94393E-03 | 3.68602E-04 |
| L/V | rs758419306 |
-1.036 | 0.012 | N | 0.17 | 0.128 | 0.457650129517 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| L/V | rs758419306 |
-1.036 | 0.012 | N | 0.17 | 0.128 | 0.457650129517 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/V | rs758419306 |
-1.036 | 0.012 | N | 0.17 | 0.128 | 0.457650129517 | gnomAD-4.0.0 | 4.06173E-06 | None | None | None | None | N | None | 1.75131E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.61549E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.2242 | likely_benign | 0.1821 | benign | -1.636 | Destabilizing | 0.525 | D | 0.381 | neutral | None | None | None | None | N |
| L/C | 0.6023 | likely_pathogenic | 0.5001 | ambiguous | -0.904 | Destabilizing | 0.998 | D | 0.453 | neutral | None | None | None | None | N |
| L/D | 0.6507 | likely_pathogenic | 0.5706 | pathogenic | -0.912 | Destabilizing | 0.728 | D | 0.51 | neutral | None | None | None | None | N |
| L/E | 0.4346 | ambiguous | 0.3635 | ambiguous | -0.88 | Destabilizing | 0.728 | D | 0.536 | neutral | None | None | None | None | N |
| L/F | 0.1861 | likely_benign | 0.1501 | benign | -1.019 | Destabilizing | 0.974 | D | 0.477 | neutral | None | None | None | None | N |
| L/G | 0.4669 | ambiguous | 0.3807 | ambiguous | -1.987 | Destabilizing | 0.842 | D | 0.505 | neutral | None | None | None | None | N |
| L/H | 0.2232 | likely_benign | 0.1808 | benign | -1.184 | Destabilizing | 0.974 | D | 0.554 | neutral | None | None | None | None | N |
| L/I | 0.1378 | likely_benign | 0.1161 | benign | -0.734 | Destabilizing | 0.669 | D | 0.33 | neutral | N | 0.499914249 | None | None | N |
| L/K | 0.2348 | likely_benign | 0.208 | benign | -1.032 | Destabilizing | 0.728 | D | 0.507 | neutral | None | None | None | None | N |
| L/M | 0.1162 | likely_benign | 0.1013 | benign | -0.588 | Destabilizing | 0.974 | D | 0.483 | neutral | None | None | None | None | N |
| L/N | 0.2501 | likely_benign | 0.2147 | benign | -0.867 | Destabilizing | 0.029 | N | 0.363 | neutral | None | None | None | None | N |
| L/P | 0.7027 | likely_pathogenic | 0.6709 | pathogenic | -1.004 | Destabilizing | 0.966 | D | 0.575 | neutral | N | 0.499914249 | None | None | N |
| L/Q | 0.1653 | likely_benign | 0.1342 | benign | -1.003 | Destabilizing | 0.267 | N | 0.386 | neutral | N | 0.482908036 | None | None | N |
| L/R | 0.1792 | likely_benign | 0.1471 | benign | -0.504 | Destabilizing | 0.934 | D | 0.54 | neutral | N | 0.483950755 | None | None | N |
| L/S | 0.2051 | likely_benign | 0.1609 | benign | -1.533 | Destabilizing | 0.172 | N | 0.363 | neutral | None | None | None | None | N |
| L/T | 0.1486 | likely_benign | 0.127 | benign | -1.384 | Destabilizing | 0.728 | D | 0.391 | neutral | None | None | None | None | N |
| L/V | 0.1304 | likely_benign | 0.1125 | benign | -1.004 | Destabilizing | 0.012 | N | 0.17 | neutral | N | 0.493310231 | None | None | N |
| L/W | 0.3215 | likely_benign | 0.2453 | benign | -1.115 | Destabilizing | 0.998 | D | 0.562 | neutral | None | None | None | None | N |
| L/Y | 0.4153 | ambiguous | 0.344 | ambiguous | -0.882 | Destabilizing | 0.991 | D | 0.511 | 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.