Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31501 | 94726;94727;94728 | chr2:178547024;178547023;178547022 | chr2:179411751;179411750;179411749 |
| N2AB | 29860 | 89803;89804;89805 | chr2:178547024;178547023;178547022 | chr2:179411751;179411750;179411749 |
| N2A | 28933 | 87022;87023;87024 | chr2:178547024;178547023;178547022 | chr2:179411751;179411750;179411749 |
| N2B | 22436 | 67531;67532;67533 | chr2:178547024;178547023;178547022 | chr2:179411751;179411750;179411749 |
| Novex-1 | 22561 | 67906;67907;67908 | chr2:178547024;178547023;178547022 | chr2:179411751;179411750;179411749 |
| Novex-2 | 22628 | 68107;68108;68109 | chr2:178547024;178547023;178547022 | chr2:179411751;179411750;179411749 |
| 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 | None | None | None | N | 0.237 | 0.087 | 0.15556083564 | gnomAD-4.0.0 | 6.84981E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00416E-07 | 0 | 0 |
| I/T | rs758756316  |
-2.273 | 0.006 | N | 0.491 | 0.158 | 0.596874347621 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.68E-05 | 0 |
| I/T | rs758756316 |
-2.273 | 0.006 | N | 0.491 | 0.158 | 0.596874347621 | gnomAD-4.0.0 | 2.55288E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.32926E-04 | None | 0 | 0 | 1.14726E-05 | 0 | 0 |
| I/V | rs780578358 |
-1.234 | None | N | 0.177 | 0.076 | 0.110078149338 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.67E-05 | 0 | 0 |
| I/V | rs780578358 |
-1.234 | None | N | 0.177 | 0.076 | 0.110078149338 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs780578358 |
-1.234 | None | N | 0.177 | 0.076 | 0.110078149338 | gnomAD-4.0.0 | 7.44366E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.40757E-04 | 0 | 2.54535E-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 | 0.1731 | likely_benign | 0.1511 | benign | -1.925 | Destabilizing | 0.003 | N | 0.486 | neutral | None | None | None | None | N |
| I/C | 0.3654 | ambiguous | 0.3718 | ambiguous | -1.185 | Destabilizing | 0.204 | N | 0.475 | neutral | None | None | None | None | N |
| I/D | 0.6917 | likely_pathogenic | 0.7052 | pathogenic | -1.812 | Destabilizing | 0.204 | N | 0.626 | neutral | None | None | None | None | N |
| I/E | 0.4665 | ambiguous | 0.5087 | ambiguous | -1.735 | Destabilizing | 0.068 | N | 0.619 | neutral | None | None | None | None | N |
| I/F | 0.1146 | likely_benign | 0.1248 | benign | -1.194 | Destabilizing | 0.018 | N | 0.505 | neutral | None | None | None | None | N |
| I/G | 0.4345 | ambiguous | 0.4108 | ambiguous | -2.318 | Highly Destabilizing | 0.035 | N | 0.579 | neutral | None | None | None | None | N |
| I/H | 0.371 | ambiguous | 0.407 | ambiguous | -1.511 | Destabilizing | 0.747 | D | 0.615 | neutral | None | None | None | None | N |
| I/K | 0.3185 | likely_benign | 0.3673 | ambiguous | -1.586 | Destabilizing | 0.026 | N | 0.593 | neutral | N | 0.474617106 | None | None | N |
| I/L | 0.0651 | likely_benign | 0.0773 | benign | -0.872 | Destabilizing | None | N | 0.237 | neutral | N | 0.476360033 | None | None | N |
| I/M | 0.0656 | likely_benign | 0.0747 | benign | -0.687 | Destabilizing | None | N | 0.351 | neutral | N | 0.475377575 | None | None | N |
| I/N | 0.2672 | likely_benign | 0.2797 | benign | -1.558 | Destabilizing | 0.204 | N | 0.618 | neutral | None | None | None | None | N |
| I/P | 0.9194 | likely_pathogenic | 0.9408 | pathogenic | -1.195 | Destabilizing | 0.439 | N | 0.632 | neutral | None | None | None | None | N |
| I/Q | 0.2598 | likely_benign | 0.2926 | benign | -1.646 | Destabilizing | 0.112 | N | 0.618 | neutral | None | None | None | None | N |
| I/R | 0.2448 | likely_benign | 0.2881 | benign | -0.999 | Destabilizing | 0.087 | N | 0.619 | neutral | N | 0.47284268 | None | None | N |
| I/S | 0.2065 | likely_benign | 0.191 | benign | -2.142 | Highly Destabilizing | 0.035 | N | 0.523 | neutral | None | None | None | None | N |
| I/T | 0.1453 | likely_benign | 0.1295 | benign | -1.942 | Destabilizing | 0.006 | N | 0.491 | neutral | N | 0.459293874 | None | None | N |
| I/V | 0.0474 | likely_benign | 0.0452 | benign | -1.195 | Destabilizing | None | N | 0.177 | neutral | N | 0.397456533 | None | None | N |
| I/W | 0.6618 | likely_pathogenic | 0.7349 | pathogenic | -1.381 | Destabilizing | 0.747 | D | 0.651 | prob.neutral | None | None | None | None | N |
| I/Y | 0.3842 | ambiguous | 0.4288 | ambiguous | -1.144 | Destabilizing | 0.204 | N | 0.553 | 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.