Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20686 | 62281;62282;62283 | chr2:178589669;178589668;178589667 | chr2:179454396;179454395;179454394 |
| N2AB | 19045 | 57358;57359;57360 | chr2:178589669;178589668;178589667 | chr2:179454396;179454395;179454394 |
| N2A | 18118 | 54577;54578;54579 | chr2:178589669;178589668;178589667 | chr2:179454396;179454395;179454394 |
| N2B | 11621 | 35086;35087;35088 | chr2:178589669;178589668;178589667 | chr2:179454396;179454395;179454394 |
| Novex-1 | 11746 | 35461;35462;35463 | chr2:178589669;178589668;178589667 | chr2:179454396;179454395;179454394 |
| Novex-2 | 11813 | 35662;35663;35664 | chr2:178589669;178589668;178589667 | chr2:179454396;179454395;179454394 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs755470129  |
-1.09 | 0.997 | N | 0.613 | 0.304 | 0.541875726618 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/C | rs755470129 |
-1.09 | 0.997 | N | 0.613 | 0.304 | 0.541875726618 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/C | rs755470129 |
-1.09 | 0.997 | N | 0.613 | 0.304 | 0.541875726618 | gnomAD-4.0.0 | 5.57827E-06 | None | None | None | None | N | None | 5.34031E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39095E-06 | 0 | 1.60133E-05 |
| Y/H | rs781138196 |
-1.676 | 0.989 | N | 0.507 | 0.24 | 0.360565625551 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.8677 | likely_pathogenic | 0.8289 | pathogenic | -2.917 | Highly Destabilizing | 0.728 | D | 0.512 | neutral | None | None | None | None | N |
| Y/C | 0.428 | ambiguous | 0.3759 | ambiguous | -1.303 | Destabilizing | 0.997 | D | 0.613 | neutral | N | 0.4752481 | None | None | N |
| Y/D | 0.9028 | likely_pathogenic | 0.8375 | pathogenic | -2.434 | Highly Destabilizing | 0.934 | D | 0.611 | neutral | N | 0.381356504 | None | None | N |
| Y/E | 0.9558 | likely_pathogenic | 0.9243 | pathogenic | -2.304 | Highly Destabilizing | 0.949 | D | 0.557 | neutral | None | None | None | None | N |
| Y/F | 0.1463 | likely_benign | 0.1314 | benign | -1.208 | Destabilizing | 0.012 | N | 0.39 | neutral | N | 0.407831029 | None | None | N |
| Y/G | 0.8777 | likely_pathogenic | 0.8469 | pathogenic | -3.27 | Highly Destabilizing | 0.842 | D | 0.548 | neutral | None | None | None | None | N |
| Y/H | 0.505 | ambiguous | 0.3986 | ambiguous | -1.642 | Destabilizing | 0.989 | D | 0.507 | neutral | N | 0.45535283 | None | None | N |
| Y/I | 0.7888 | likely_pathogenic | 0.7095 | pathogenic | -1.781 | Destabilizing | 0.728 | D | 0.434 | neutral | None | None | None | None | N |
| Y/K | 0.9276 | likely_pathogenic | 0.8858 | pathogenic | -1.864 | Destabilizing | 0.949 | D | 0.561 | neutral | None | None | None | None | N |
| Y/L | 0.6141 | likely_pathogenic | 0.569 | pathogenic | -1.781 | Destabilizing | 0.016 | N | 0.339 | neutral | None | None | None | None | N |
| Y/M | 0.7871 | likely_pathogenic | 0.7349 | pathogenic | -1.245 | Destabilizing | 0.949 | D | 0.553 | neutral | None | None | None | None | N |
| Y/N | 0.6562 | likely_pathogenic | 0.5407 | ambiguous | -2.351 | Highly Destabilizing | 0.934 | D | 0.579 | neutral | N | 0.421856332 | None | None | N |
| Y/P | 0.9949 | likely_pathogenic | 0.9929 | pathogenic | -2.166 | Highly Destabilizing | 0.974 | D | 0.646 | neutral | None | None | None | None | N |
| Y/Q | 0.8967 | likely_pathogenic | 0.8393 | pathogenic | -2.252 | Highly Destabilizing | 0.974 | D | 0.546 | neutral | None | None | None | None | N |
| Y/R | 0.8518 | likely_pathogenic | 0.7805 | pathogenic | -1.37 | Destabilizing | 0.974 | D | 0.596 | neutral | None | None | None | None | N |
| Y/S | 0.6113 | likely_pathogenic | 0.5394 | ambiguous | -2.762 | Highly Destabilizing | 0.267 | N | 0.464 | neutral | N | 0.409252394 | None | None | N |
| Y/T | 0.7853 | likely_pathogenic | 0.7245 | pathogenic | -2.539 | Highly Destabilizing | 0.728 | D | 0.507 | neutral | None | None | None | None | N |
| Y/V | 0.6911 | likely_pathogenic | 0.6186 | pathogenic | -2.166 | Highly Destabilizing | 0.728 | D | 0.443 | neutral | None | None | None | None | N |
| Y/W | 0.6222 | likely_pathogenic | 0.6063 | pathogenic | -0.693 | Destabilizing | 0.998 | D | 0.501 | 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.