Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31435 | 94528;94529;94530 | chr2:178547222;178547221;178547220 | chr2:179411949;179411948;179411947 |
| N2AB | 29794 | 89605;89606;89607 | chr2:178547222;178547221;178547220 | chr2:179411949;179411948;179411947 |
| N2A | 28867 | 86824;86825;86826 | chr2:178547222;178547221;178547220 | chr2:179411949;179411948;179411947 |
| N2B | 22370 | 67333;67334;67335 | chr2:178547222;178547221;178547220 | chr2:179411949;179411948;179411947 |
| Novex-1 | 22495 | 67708;67709;67710 | chr2:178547222;178547221;178547220 | chr2:179411949;179411948;179411947 |
| Novex-2 | 22562 | 67909;67910;67911 | chr2:178547222;178547221;178547220 | chr2:179411949;179411948;179411947 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs1271635080  |
-0.746 | 1.0 | N | 0.687 | 0.53 | 0.435915822735 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| D/G | rs1271635080 |
-0.746 | 1.0 | N | 0.687 | 0.53 | 0.435915822735 | gnomAD-4.0.0 | 6.84213E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99489E-06 | 0 | 0 |
| D/N | rs367771286 |
-0.538 | 1.0 | N | 0.69 | 0.393 | None | gnomAD-2.1.1 | 6.43E-05 | None | None | None | None | I | None | 1.23977E-04 | 2.83E-05 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 9.38E-05 | 0 |
| D/N | rs367771286 |
-0.538 | 1.0 | N | 0.69 | 0.393 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | I | None | 9.65E-05 | 6.54E-05 | 0 | 0 | 0 | None | 9.43E-05 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs367771286 |
-0.538 | 1.0 | N | 0.69 | 0.393 | None | gnomAD-4.0.0 | 6.44479E-05 | None | None | None | None | I | None | 8.00961E-05 | 3.33322E-05 | None | 0 | 2.22806E-05 | None | 4.68677E-05 | 0 | 7.20481E-05 | 4.39126E-05 | 4.80354E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.8528 | likely_pathogenic | 0.877 | pathogenic | -0.308 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | N | 0.493551644 | None | None | I |
| D/C | 0.9673 | likely_pathogenic | 0.9714 | pathogenic | 0.03 | Stabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | I |
| D/E | 0.856 | likely_pathogenic | 0.8684 | pathogenic | -0.706 | Destabilizing | 1.0 | D | 0.441 | neutral | N | 0.496816874 | None | None | I |
| D/F | 0.985 | likely_pathogenic | 0.9875 | pathogenic | -0.538 | Destabilizing | 1.0 | D | 0.644 | neutral | None | None | None | None | I |
| D/G | 0.7899 | likely_pathogenic | 0.8198 | pathogenic | -0.584 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | N | 0.514493509 | None | None | I |
| D/H | 0.8881 | likely_pathogenic | 0.8931 | pathogenic | -0.968 | Destabilizing | 1.0 | D | 0.651 | neutral | N | 0.502376735 | None | None | I |
| D/I | 0.9666 | likely_pathogenic | 0.9735 | pathogenic | 0.389 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | I |
| D/K | 0.9591 | likely_pathogenic | 0.9641 | pathogenic | -0.167 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| D/L | 0.9519 | likely_pathogenic | 0.9604 | pathogenic | 0.389 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| D/M | 0.9793 | likely_pathogenic | 0.9827 | pathogenic | 0.877 | Stabilizing | 1.0 | D | 0.634 | neutral | None | None | None | None | I |
| D/N | 0.1685 | likely_benign | 0.1884 | benign | -0.422 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | N | 0.471586275 | None | None | I |
| D/P | 0.9763 | likely_pathogenic | 0.9748 | pathogenic | 0.182 | Stabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| D/Q | 0.9454 | likely_pathogenic | 0.9479 | pathogenic | -0.336 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | I |
| D/R | 0.9579 | likely_pathogenic | 0.9621 | pathogenic | -0.256 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | I |
| D/S | 0.4334 | ambiguous | 0.4664 | ambiguous | -0.603 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| D/T | 0.6531 | likely_pathogenic | 0.6864 | pathogenic | -0.382 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | I |
| D/V | 0.9124 | likely_pathogenic | 0.9288 | pathogenic | 0.182 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | N | 0.513226062 | None | None | I |
| D/W | 0.9967 | likely_pathogenic | 0.9971 | pathogenic | -0.57 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| D/Y | 0.8909 | likely_pathogenic | 0.9114 | pathogenic | -0.353 | Destabilizing | 1.0 | D | 0.624 | neutral | D | 0.537370704 | 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.