Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5062 | 15409;15410;15411 | chr2:178734740;178734739;178734738 | chr2:179599467;179599466;179599465 |
| N2AB | 4745 | 14458;14459;14460 | chr2:178734740;178734739;178734738 | chr2:179599467;179599466;179599465 |
| N2A | 3818 | 11677;11678;11679 | chr2:178734740;178734739;178734738 | chr2:179599467;179599466;179599465 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/G | rs778610579  |
-0.67 | 0.669 | D | 0.313 | 0.299 | 0.26169431596 | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | I | None | 0 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 1.60527E-04 | 1.56E-05 | 0 |
| S/G | rs778610579 |
-0.67 | 0.669 | D | 0.313 | 0.299 | 0.26169431596 | gnomAD-4.0.0 | 1.11529E-05 | None | None | None | None | I | None | 0 | 2.28676E-05 | None | 0 | 0 | None | 5.65099E-05 | 0 | 5.72738E-06 | 0 | 3.0259E-05 |
| S/I | rs371687650 |
0.012 | 0.934 | D | 0.557 | 0.323 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/I | rs371687650 |
0.012 | 0.934 | D | 0.557 | 0.323 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 7.24E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/I | rs371687650 |
0.012 | 0.934 | D | 0.557 | 0.323 | None | gnomAD-4.0.0 | 6.20027E-06 | None | None | None | None | I | None | 1.06789E-04 | 1.66744E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60179E-05 |
| S/N | rs371687650 |
-0.213 | 0.012 | D | 0.218 | 0.224 | None | gnomAD-2.1.1 | 7.86E-05 | None | None | None | None | I | None | 0 | 2.83E-05 | None | 1.16234E-03 | 0 | None | 0 | None | 0 | 5.48E-05 | 2.81452E-04 |
| S/N | rs371687650 |
-0.213 | 0.012 | D | 0.218 | 0.224 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 1.44009E-03 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | rs371687650 |
-0.213 | 0.012 | D | 0.218 | 0.224 | None | gnomAD-4.0.0 | 3.03813E-05 | None | None | None | None | I | None | 0 | 1.66744E-05 | None | 9.80127E-04 | 0 | None | 0 | 0 | 1.10256E-05 | 0 | 9.61076E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0904 | likely_benign | 0.0866 | benign | -0.417 | Destabilizing | 0.525 | D | 0.393 | neutral | None | None | None | None | I |
| S/C | 0.1253 | likely_benign | 0.1198 | benign | -0.319 | Destabilizing | 0.012 | N | 0.273 | neutral | D | 0.548189717 | None | None | I |
| S/D | 0.4405 | ambiguous | 0.5005 | ambiguous | -0.123 | Destabilizing | 0.728 | D | 0.381 | neutral | None | None | None | None | I |
| S/E | 0.4808 | ambiguous | 0.5184 | ambiguous | -0.219 | Destabilizing | 0.842 | D | 0.39 | neutral | None | None | None | None | I |
| S/F | 0.2069 | likely_benign | 0.2148 | benign | -0.952 | Destabilizing | 0.991 | D | 0.568 | neutral | None | None | None | None | I |
| S/G | 0.1023 | likely_benign | 0.1064 | benign | -0.535 | Destabilizing | 0.669 | D | 0.313 | neutral | D | 0.633693056 | None | None | I |
| S/H | 0.2695 | likely_benign | 0.3009 | benign | -1.04 | Destabilizing | 0.993 | D | 0.472 | neutral | None | None | None | None | I |
| S/I | 0.1863 | likely_benign | 0.179 | benign | -0.231 | Destabilizing | 0.934 | D | 0.557 | neutral | D | 0.566702751 | None | None | I |
| S/K | 0.4495 | ambiguous | 0.4578 | ambiguous | -0.606 | Destabilizing | 0.842 | D | 0.388 | neutral | None | None | None | None | I |
| S/L | 0.1228 | likely_benign | 0.1218 | benign | -0.231 | Destabilizing | 0.728 | D | 0.507 | neutral | None | None | None | None | I |
| S/M | 0.1903 | likely_benign | 0.1984 | benign | 0.088 | Stabilizing | 0.998 | D | 0.471 | neutral | None | None | None | None | I |
| S/N | 0.1306 | likely_benign | 0.1377 | benign | -0.306 | Destabilizing | 0.012 | N | 0.218 | neutral | D | 0.575556789 | None | None | I |
| S/P | 0.7424 | likely_pathogenic | 0.7979 | pathogenic | -0.264 | Destabilizing | 0.991 | D | 0.484 | neutral | None | None | None | None | I |
| S/Q | 0.3797 | ambiguous | 0.4045 | ambiguous | -0.616 | Destabilizing | 0.974 | D | 0.427 | neutral | None | None | None | None | I |
| S/R | 0.3477 | ambiguous | 0.3611 | ambiguous | -0.331 | Destabilizing | 0.934 | D | 0.484 | neutral | D | 0.540898263 | None | None | I |
| S/T | 0.0766 | likely_benign | 0.0805 | benign | -0.416 | Destabilizing | 0.051 | N | 0.193 | neutral | N | 0.512166585 | None | None | I |
| S/V | 0.1854 | likely_benign | 0.1806 | benign | -0.264 | Destabilizing | 0.842 | D | 0.529 | neutral | None | None | None | None | I |
| S/W | 0.3385 | likely_benign | 0.3849 | ambiguous | -0.931 | Destabilizing | 0.998 | D | 0.619 | neutral | None | None | None | None | I |
| S/Y | 0.1986 | likely_benign | 0.2164 | benign | -0.672 | Destabilizing | 0.991 | D | 0.569 | neutral | None | None | 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.