Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2448 | 7567;7568;7569 | chr2:178773714;178773713;178773712 | chr2:179638441;179638440;179638439 |
| N2AB | 2448 | 7567;7568;7569 | chr2:178773714;178773713;178773712 | chr2:179638441;179638440;179638439 |
| N2A | 2448 | 7567;7568;7569 | chr2:178773714;178773713;178773712 | chr2:179638441;179638440;179638439 |
| N2B | 2402 | 7429;7430;7431 | chr2:178773714;178773713;178773712 | chr2:179638441;179638440;179638439 |
| Novex-1 | 2402 | 7429;7430;7431 | chr2:178773714;178773713;178773712 | chr2:179638441;179638440;179638439 |
| Novex-2 | 2402 | 7429;7430;7431 | chr2:178773714;178773713;178773712 | chr2:179638441;179638440;179638439 |
| Novex-3 | 2448 | 7567;7568;7569 | chr2:178773714;178773713;178773712 | chr2:179638441;179638440;179638439 |
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/V | rs143616825  |
-0.69 | None | N | 0.088 | 0.074 | None | gnomAD-2.1.1 | 7.98E-06 | None | None | None | None | I | None | 0 | 5.79E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs143616825 |
-0.69 | None | N | 0.088 | 0.074 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 2.61883E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs143616825 |
-0.69 | None | N | 0.088 | 0.074 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | I | None | 0 | 2.9E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/V | rs143616825 |
-0.69 | None | N | 0.088 | 0.074 | None | gnomAD-4.0.0 | 1.28041E-05 | None | None | None | None | I | None | 0 | 1.18608E-04 | None | 0 | 0 | None | 0 | 0 | 4.78364E-06 | 0 | 2.84026E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.333 | likely_benign | 0.3233 | benign | -1.051 | Destabilizing | 0.001 | N | 0.151 | neutral | None | None | None | None | I |
| I/C | 0.7075 | likely_pathogenic | 0.7094 | pathogenic | -0.701 | Destabilizing | 0.824 | D | 0.349 | neutral | None | None | None | None | I |
| I/D | 0.6728 | likely_pathogenic | 0.6768 | pathogenic | -0.527 | Destabilizing | 0.555 | D | 0.385 | neutral | None | None | None | None | I |
| I/E | 0.5132 | ambiguous | 0.5219 | ambiguous | -0.606 | Destabilizing | 0.555 | D | 0.365 | neutral | None | None | None | None | I |
| I/F | 0.2125 | likely_benign | 0.2107 | benign | -0.895 | Destabilizing | 0.235 | N | 0.353 | neutral | None | None | None | None | I |
| I/G | 0.6579 | likely_pathogenic | 0.6439 | pathogenic | -1.258 | Destabilizing | 0.149 | N | 0.345 | neutral | None | None | None | None | I |
| I/H | 0.5311 | ambiguous | 0.5401 | ambiguous | -0.426 | Destabilizing | 0.935 | D | 0.331 | neutral | None | None | None | None | I |
| I/K | 0.3671 | ambiguous | 0.3866 | ambiguous | -0.677 | Destabilizing | 0.484 | N | 0.362 | neutral | N | 0.434565078 | None | None | I |
| I/L | 0.1133 | likely_benign | 0.1103 | benign | -0.612 | Destabilizing | None | N | 0.083 | neutral | N | 0.416265664 | None | None | I |
| I/M | 0.1109 | likely_benign | 0.1085 | benign | -0.459 | Destabilizing | 0.188 | N | 0.383 | neutral | N | 0.480818406 | None | None | I |
| I/N | 0.2658 | likely_benign | 0.2678 | benign | -0.456 | Destabilizing | 0.791 | D | 0.368 | neutral | None | None | None | None | I |
| I/P | 0.8472 | likely_pathogenic | 0.8448 | pathogenic | -0.725 | Destabilizing | 0.555 | D | 0.383 | neutral | None | None | None | None | I |
| I/Q | 0.4216 | ambiguous | 0.4282 | ambiguous | -0.717 | Destabilizing | 0.791 | D | 0.359 | neutral | None | None | None | None | I |
| I/R | 0.3321 | likely_benign | 0.355 | ambiguous | -0.007 | Destabilizing | 0.484 | N | 0.374 | neutral | N | 0.451462349 | None | None | I |
| I/S | 0.3068 | likely_benign | 0.3065 | benign | -0.954 | Destabilizing | 0.081 | N | 0.265 | neutral | None | None | None | None | I |
| I/T | 0.2101 | likely_benign | 0.2142 | benign | -0.929 | Destabilizing | 0.117 | N | 0.298 | neutral | N | 0.447422438 | None | None | I |
| I/V | 0.0787 | likely_benign | 0.077 | benign | -0.725 | Destabilizing | None | N | 0.088 | neutral | N | 0.426745493 | None | None | I |
| I/W | 0.8406 | likely_pathogenic | 0.8478 | pathogenic | -0.886 | Destabilizing | 0.935 | D | 0.398 | neutral | None | None | None | None | I |
| I/Y | 0.5575 | ambiguous | 0.5663 | pathogenic | -0.672 | Destabilizing | 0.555 | D | 0.394 | 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.