Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29605 | 89038;89039;89040 | chr2:178554534;178554533;178554532 | chr2:179419261;179419260;179419259 |
| N2AB | 27964 | 84115;84116;84117 | chr2:178554534;178554533;178554532 | chr2:179419261;179419260;179419259 |
| N2A | 27037 | 81334;81335;81336 | chr2:178554534;178554533;178554532 | chr2:179419261;179419260;179419259 |
| N2B | 20540 | 61843;61844;61845 | chr2:178554534;178554533;178554532 | chr2:179419261;179419260;179419259 |
| Novex-1 | 20665 | 62218;62219;62220 | chr2:178554534;178554533;178554532 | chr2:179419261;179419260;179419259 |
| Novex-2 | 20732 | 62419;62420;62421 | chr2:178554534;178554533;178554532 | chr2:179419261;179419260;179419259 |
| 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 | rs755867567  |
-0.37 | 0.025 | N | 0.465 | 0.086 | 0.141422826196 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| I/N | rs906583017 |
-1.797 | 0.667 | N | 0.763 | 0.299 | 0.530011692926 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| I/N | rs906583017 |
-1.797 | 0.667 | N | 0.763 | 0.299 | 0.530011692926 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/N | rs906583017 |
-1.797 | 0.667 | N | 0.763 | 0.299 | 0.530011692926 | gnomAD-4.0.0 | 1.31506E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.94048E-05 | 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 | 0.3327 | likely_benign | 0.3346 | benign | -2.685 | Highly Destabilizing | 0.072 | N | 0.643 | neutral | None | None | None | None | N |
| I/C | 0.5357 | ambiguous | 0.5171 | ambiguous | -1.666 | Destabilizing | 0.909 | D | 0.707 | prob.neutral | None | None | None | None | N |
| I/D | 0.7719 | likely_pathogenic | 0.7791 | pathogenic | -3.012 | Highly Destabilizing | 0.567 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/E | 0.5941 | likely_pathogenic | 0.5707 | pathogenic | -2.738 | Highly Destabilizing | 0.157 | N | 0.707 | prob.neutral | None | None | None | None | N |
| I/F | 0.2169 | likely_benign | 0.2243 | benign | -1.503 | Destabilizing | 0.497 | N | 0.694 | prob.neutral | N | 0.473093229 | None | None | N |
| I/G | 0.658 | likely_pathogenic | 0.66 | pathogenic | -3.219 | Highly Destabilizing | 0.726 | D | 0.709 | prob.delet. | None | None | None | None | N |
| I/H | 0.4325 | ambiguous | 0.4314 | ambiguous | -2.737 | Highly Destabilizing | 0.909 | D | 0.785 | deleterious | None | None | None | None | N |
| I/K | 0.3768 | ambiguous | 0.3537 | ambiguous | -1.73 | Destabilizing | 0.396 | N | 0.711 | prob.delet. | None | None | None | None | N |
| I/L | 0.1068 | likely_benign | 0.1106 | benign | -1.093 | Destabilizing | 0.025 | N | 0.465 | neutral | N | 0.47328523 | None | None | N |
| I/M | 0.1165 | likely_benign | 0.1181 | benign | -1.226 | Destabilizing | 0.497 | N | 0.69 | prob.neutral | N | 0.489428118 | None | None | N |
| I/N | 0.3006 | likely_benign | 0.2957 | benign | -2.226 | Highly Destabilizing | 0.667 | D | 0.763 | deleterious | N | 0.501354479 | None | None | N |
| I/P | 0.9777 | likely_pathogenic | 0.9808 | pathogenic | -1.613 | Destabilizing | 0.726 | D | 0.759 | deleterious | None | None | None | None | N |
| I/Q | 0.3643 | ambiguous | 0.3466 | ambiguous | -1.976 | Destabilizing | 0.033 | N | 0.626 | neutral | None | None | None | None | N |
| I/R | 0.2889 | likely_benign | 0.2809 | benign | -1.673 | Destabilizing | 0.567 | D | 0.752 | deleterious | None | None | None | None | N |
| I/S | 0.2721 | likely_benign | 0.2674 | benign | -2.806 | Highly Destabilizing | 0.497 | N | 0.693 | prob.neutral | N | 0.488251895 | None | None | N |
| I/T | 0.1731 | likely_benign | 0.1744 | benign | -2.396 | Highly Destabilizing | 0.124 | N | 0.68 | prob.neutral | N | 0.450578942 | None | None | N |
| I/V | 0.0613 | likely_benign | 0.0606 | benign | -1.613 | Destabilizing | None | N | 0.245 | neutral | N | 0.454294037 | None | None | N |
| I/W | 0.8375 | likely_pathogenic | 0.8391 | pathogenic | -1.858 | Destabilizing | 0.968 | D | 0.785 | deleterious | None | None | None | None | N |
| I/Y | 0.5399 | ambiguous | 0.5367 | ambiguous | -1.659 | Destabilizing | 0.726 | D | 0.724 | prob.delet. | 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.