Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2387 | 7384;7385;7386 | chr2:178774009;178774008;178774007 | chr2:179638736;179638735;179638734 |
| N2AB | 2387 | 7384;7385;7386 | chr2:178774009;178774008;178774007 | chr2:179638736;179638735;179638734 |
| N2A | 2387 | 7384;7385;7386 | chr2:178774009;178774008;178774007 | chr2:179638736;179638735;179638734 |
| N2B | 2341 | 7246;7247;7248 | chr2:178774009;178774008;178774007 | chr2:179638736;179638735;179638734 |
| Novex-1 | 2341 | 7246;7247;7248 | chr2:178774009;178774008;178774007 | chr2:179638736;179638735;179638734 |
| Novex-2 | 2341 | 7246;7247;7248 | chr2:178774009;178774008;178774007 | chr2:179638736;179638735;179638734 |
| Novex-3 | 2387 | 7384;7385;7386 | chr2:178774009;178774008;178774007 | chr2:179638736;179638735;179638734 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs377691143  |
-0.383 | 0.008 | N | 0.241 | 0.044 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 1.98768E-04 | 1.08873E-04 | None | 6.53E-05 | None | 0 | 1.76E-05 | 0 |
| V/I | rs377691143 |
-0.383 | 0.008 | N | 0.241 | 0.044 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 2.88351E-04 | 0 | None | 0 | 0 | 4.41E-05 | 2.07211E-04 | 0 |
| V/I | rs377691143 |
-0.383 | 0.008 | N | 0.241 | 0.044 | None | gnomAD-4.0.0 | 1.85877E-05 | None | None | None | None | N | None | 1.33472E-05 | 0 | None | 1.01338E-04 | 4.45593E-05 | None | 0 | 0 | 1.52543E-05 | 3.29366E-05 | 4.80108E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1359 | likely_benign | 0.1318 | benign | -1.608 | Destabilizing | 0.165 | N | 0.497 | neutral | N | 0.507677465 | None | None | N |
| V/C | 0.4748 | ambiguous | 0.4397 | ambiguous | -0.778 | Destabilizing | 0.981 | D | 0.521 | neutral | None | None | None | None | N |
| V/D | 0.2521 | likely_benign | 0.2516 | benign | -1.544 | Destabilizing | 0.627 | D | 0.63 | neutral | D | 0.538513126 | None | None | N |
| V/E | 0.1841 | likely_benign | 0.1826 | benign | -1.482 | Destabilizing | 0.241 | N | 0.567 | neutral | None | None | None | None | N |
| V/F | 0.0926 | likely_benign | 0.0898 | benign | -1.124 | Destabilizing | 0.81 | D | 0.556 | neutral | N | 0.510954847 | None | None | N |
| V/G | 0.1733 | likely_benign | 0.1696 | benign | -1.99 | Destabilizing | 0.492 | N | 0.608 | neutral | N | 0.510702151 | None | None | N |
| V/H | 0.2715 | likely_benign | 0.2546 | benign | -1.585 | Destabilizing | 0.944 | D | 0.634 | neutral | None | None | None | None | N |
| V/I | 0.0581 | likely_benign | 0.0571 | benign | -0.625 | Destabilizing | 0.008 | N | 0.241 | neutral | N | 0.485673594 | None | None | N |
| V/K | 0.1485 | likely_benign | 0.141 | benign | -1.256 | Destabilizing | 0.241 | N | 0.569 | neutral | None | None | None | None | N |
| V/L | 0.1009 | likely_benign | 0.0999 | benign | -0.625 | Destabilizing | 0.08 | N | 0.482 | neutral | N | 0.502341142 | None | None | N |
| V/M | 0.0864 | likely_benign | 0.0833 | benign | -0.356 | Destabilizing | 0.69 | D | 0.529 | neutral | None | None | None | None | N |
| V/N | 0.1194 | likely_benign | 0.1148 | benign | -1.103 | Destabilizing | 0.818 | D | 0.631 | neutral | None | None | None | None | N |
| V/P | 0.8153 | likely_pathogenic | 0.8316 | pathogenic | -0.92 | Destabilizing | 0.932 | D | 0.591 | neutral | None | None | None | None | N |
| V/Q | 0.1667 | likely_benign | 0.1603 | benign | -1.192 | Destabilizing | 0.054 | N | 0.452 | neutral | None | None | None | None | N |
| V/R | 0.1362 | likely_benign | 0.1293 | benign | -0.814 | Destabilizing | 0.69 | D | 0.635 | neutral | None | None | None | None | N |
| V/S | 0.1241 | likely_benign | 0.12 | benign | -1.646 | Destabilizing | 0.241 | N | 0.587 | neutral | None | None | None | None | N |
| V/T | 0.1044 | likely_benign | 0.1009 | benign | -1.471 | Destabilizing | 0.004 | N | 0.213 | neutral | None | None | None | None | N |
| V/W | 0.5818 | likely_pathogenic | 0.56 | ambiguous | -1.443 | Destabilizing | 0.981 | D | 0.673 | neutral | None | None | None | None | N |
| V/Y | 0.2955 | likely_benign | 0.2865 | benign | -1.11 | Destabilizing | 0.818 | D | 0.549 | neutral | 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.