Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21100 | 63523;63524;63525 | chr2:178588109;178588108;178588107 | chr2:179452836;179452835;179452834 |
| N2AB | 19459 | 58600;58601;58602 | chr2:178588109;178588108;178588107 | chr2:179452836;179452835;179452834 |
| N2A | 18532 | 55819;55820;55821 | chr2:178588109;178588108;178588107 | chr2:179452836;179452835;179452834 |
| N2B | 12035 | 36328;36329;36330 | chr2:178588109;178588108;178588107 | chr2:179452836;179452835;179452834 |
| Novex-1 | 12160 | 36703;36704;36705 | chr2:178588109;178588108;178588107 | chr2:179452836;179452835;179452834 |
| Novex-2 | 12227 | 36904;36905;36906 | chr2:178588109;178588108;178588107 | chr2:179452836;179452835;179452834 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.027 | N | 0.585 | 0.126 | 0.580120749226 | gnomAD-4.0.0 | 6.84561E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.998E-07 | 0 | 0 |
| V/I | rs774240012  |
-0.785 | None | N | 0.279 | 0.045 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/I | rs774240012 |
-0.785 | None | N | 0.279 | 0.045 | None | gnomAD-4.0.0 | 1.36912E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.32002E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4094 | ambiguous | 0.3626 | ambiguous | -2.306 | Highly Destabilizing | 0.027 | N | 0.585 | neutral | N | 0.521865824 | None | None | N |
| V/C | 0.758 | likely_pathogenic | 0.7235 | pathogenic | -1.99 | Destabilizing | 0.935 | D | 0.673 | neutral | None | None | None | None | N |
| V/D | 0.7948 | likely_pathogenic | 0.7125 | pathogenic | -3.023 | Highly Destabilizing | 0.317 | N | 0.711 | prob.delet. | N | 0.519268236 | None | None | N |
| V/E | 0.646 | likely_pathogenic | 0.5561 | ambiguous | -2.864 | Highly Destabilizing | 0.149 | N | 0.678 | prob.neutral | None | None | None | None | N |
| V/F | 0.2628 | likely_benign | 0.2166 | benign | -1.448 | Destabilizing | 0.317 | N | 0.719 | prob.delet. | N | 0.495623372 | None | None | N |
| V/G | 0.6134 | likely_pathogenic | 0.5496 | ambiguous | -2.778 | Highly Destabilizing | 0.117 | N | 0.691 | prob.neutral | N | 0.492435554 | None | None | N |
| V/H | 0.7452 | likely_pathogenic | 0.6836 | pathogenic | -2.325 | Highly Destabilizing | 0.935 | D | 0.701 | prob.neutral | None | None | None | None | N |
| V/I | 0.0746 | likely_benign | 0.0724 | benign | -1.009 | Destabilizing | None | N | 0.279 | neutral | N | 0.417066588 | None | None | N |
| V/K | 0.7465 | likely_pathogenic | 0.6694 | pathogenic | -1.983 | Destabilizing | 0.149 | N | 0.681 | prob.neutral | None | None | None | None | N |
| V/L | 0.2093 | likely_benign | 0.1717 | benign | -1.009 | Destabilizing | None | N | 0.309 | neutral | N | 0.460009288 | None | None | N |
| V/M | 0.1894 | likely_benign | 0.1624 | benign | -1.084 | Destabilizing | 0.38 | N | 0.701 | prob.neutral | None | None | None | None | N |
| V/N | 0.6341 | likely_pathogenic | 0.5492 | ambiguous | -2.209 | Highly Destabilizing | 0.38 | N | 0.712 | prob.delet. | None | None | None | None | N |
| V/P | 0.9861 | likely_pathogenic | 0.9824 | pathogenic | -1.415 | Destabilizing | 0.555 | D | 0.668 | neutral | None | None | None | None | N |
| V/Q | 0.6173 | likely_pathogenic | 0.5449 | ambiguous | -2.179 | Highly Destabilizing | 0.555 | D | 0.664 | neutral | None | None | None | None | N |
| V/R | 0.6531 | likely_pathogenic | 0.566 | pathogenic | -1.587 | Destabilizing | 0.555 | D | 0.709 | prob.delet. | None | None | None | None | N |
| V/S | 0.5097 | ambiguous | 0.4403 | ambiguous | -2.786 | Highly Destabilizing | 0.003 | N | 0.523 | neutral | None | None | None | None | N |
| V/T | 0.3273 | likely_benign | 0.2883 | benign | -2.503 | Highly Destabilizing | 0.081 | N | 0.653 | neutral | None | None | None | None | N |
| V/W | 0.85 | likely_pathogenic | 0.7918 | pathogenic | -1.879 | Destabilizing | 0.935 | D | 0.71 | prob.delet. | None | None | None | None | N |
| V/Y | 0.6583 | likely_pathogenic | 0.5741 | pathogenic | -1.58 | Destabilizing | 0.555 | D | 0.709 | 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.