Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29991 | 90196;90197;90198 | chr2:178552929;178552928;178552927 | chr2:179417656;179417655;179417654 |
| N2AB | 28350 | 85273;85274;85275 | chr2:178552929;178552928;178552927 | chr2:179417656;179417655;179417654 |
| N2A | 27423 | 82492;82493;82494 | chr2:178552929;178552928;178552927 | chr2:179417656;179417655;179417654 |
| N2B | 20926 | 63001;63002;63003 | chr2:178552929;178552928;178552927 | chr2:179417656;179417655;179417654 |
| Novex-1 | 21051 | 63376;63377;63378 | chr2:178552929;178552928;178552927 | chr2:179417656;179417655;179417654 |
| Novex-2 | 21118 | 63577;63578;63579 | chr2:178552929;178552928;178552927 | chr2:179417656;179417655;179417654 |
| 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/F | rs879239139  |
-0.702 | 0.879 | N | 0.697 | 0.428 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14837E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/F | rs879239139 |
-0.702 | 0.879 | N | 0.697 | 0.428 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/F | rs879239139 |
-0.702 | 0.879 | N | 0.697 | 0.428 | None | gnomAD-4.0.0 | 5.12535E-06 | None | None | None | None | I | None | 6.76865E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | rs777975852 |
-0.014 | None | N | 0.213 | 0.121 | 0.0551355673512 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| S/T | rs777975852 |
-0.014 | None | N | 0.213 | 0.121 | 0.0551355673512 | gnomAD-4.0.0 | 1.5914E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85796E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0858 | likely_benign | 0.0861 | benign | -0.639 | Destabilizing | 0.174 | N | 0.401 | neutral | N | 0.500517084 | None | None | I |
| S/C | 0.1227 | likely_benign | 0.1176 | benign | -0.27 | Destabilizing | 0.965 | D | 0.629 | neutral | N | 0.512508954 | None | None | I |
| S/D | 0.5897 | likely_pathogenic | 0.5912 | pathogenic | 0.214 | Stabilizing | 0.575 | D | 0.443 | neutral | None | None | None | None | I |
| S/E | 0.6583 | likely_pathogenic | 0.6773 | pathogenic | 0.278 | Stabilizing | 0.575 | D | 0.429 | neutral | None | None | None | None | I |
| S/F | 0.2034 | likely_benign | 0.2129 | benign | -0.738 | Destabilizing | 0.879 | D | 0.697 | prob.neutral | N | 0.500138691 | None | None | I |
| S/G | 0.1293 | likely_benign | 0.1255 | benign | -0.944 | Destabilizing | 0.575 | D | 0.457 | neutral | None | None | None | None | I |
| S/H | 0.3717 | ambiguous | 0.3834 | ambiguous | -1.268 | Destabilizing | 0.991 | D | 0.628 | neutral | None | None | None | None | I |
| S/I | 0.1796 | likely_benign | 0.182 | benign | 0.079 | Stabilizing | 0.704 | D | 0.631 | neutral | None | None | None | None | I |
| S/K | 0.7454 | likely_pathogenic | 0.7681 | pathogenic | -0.179 | Destabilizing | 0.575 | D | 0.44 | neutral | None | None | None | None | I |
| S/L | 0.1189 | likely_benign | 0.12 | benign | 0.079 | Stabilizing | 0.404 | N | 0.588 | neutral | None | None | None | None | I |
| S/M | 0.1812 | likely_benign | 0.1899 | benign | 0.107 | Stabilizing | 0.973 | D | 0.634 | neutral | None | None | None | None | I |
| S/N | 0.1653 | likely_benign | 0.1659 | benign | -0.334 | Destabilizing | 0.575 | D | 0.433 | neutral | None | None | None | None | I |
| S/P | 0.8016 | likely_pathogenic | 0.7988 | pathogenic | -0.125 | Destabilizing | 0.879 | D | 0.583 | neutral | N | 0.519888787 | None | None | I |
| S/Q | 0.5283 | ambiguous | 0.5345 | ambiguous | -0.302 | Destabilizing | 0.906 | D | 0.527 | neutral | None | None | None | None | I |
| S/R | 0.6696 | likely_pathogenic | 0.7004 | pathogenic | -0.283 | Destabilizing | 0.826 | D | 0.59 | neutral | None | None | None | None | I |
| S/T | 0.0655 | likely_benign | 0.0673 | benign | -0.326 | Destabilizing | None | N | 0.213 | neutral | N | 0.474672096 | None | None | I |
| S/V | 0.1653 | likely_benign | 0.1616 | benign | -0.125 | Destabilizing | 0.404 | N | 0.577 | neutral | None | None | None | None | I |
| S/W | 0.4291 | ambiguous | 0.4342 | ambiguous | -0.78 | Destabilizing | 0.991 | D | 0.766 | deleterious | None | None | None | None | I |
| S/Y | 0.2021 | likely_benign | 0.209 | benign | -0.434 | Destabilizing | 0.879 | D | 0.701 | prob.neutral | N | 0.520142277 | 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.