Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24742 | 74449;74450;74451 | chr2:178571908;178571907;178571906 | chr2:179436635;179436634;179436633 |
| N2AB | 23101 | 69526;69527;69528 | chr2:178571908;178571907;178571906 | chr2:179436635;179436634;179436633 |
| N2A | 22174 | 66745;66746;66747 | chr2:178571908;178571907;178571906 | chr2:179436635;179436634;179436633 |
| N2B | 15677 | 47254;47255;47256 | chr2:178571908;178571907;178571906 | chr2:179436635;179436634;179436633 |
| Novex-1 | 15802 | 47629;47630;47631 | chr2:178571908;178571907;178571906 | chr2:179436635;179436634;179436633 |
| Novex-2 | 15869 | 47830;47831;47832 | chr2:178571908;178571907;178571906 | chr2:179436635;179436634;179436633 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs369489704  |
-0.262 | 0.017 | N | 0.397 | 0.31 | None | gnomAD-2.1.1 | 3.23E-05 | None | None | None | None | I | None | 0 | 8.71E-05 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 2.67E-05 | 0 |
| R/C | rs369489704 |
-0.262 | 0.017 | N | 0.397 | 0.31 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs369489704 |
-0.262 | 0.017 | N | 0.397 | 0.31 | None | gnomAD-4.0.0 | 1.54978E-05 | None | None | None | None | I | None | 1.33576E-05 | 5.00417E-05 | None | 0 | 0 | None | 0 | 0 | 1.10211E-05 | 7.68808E-05 | 1.60205E-05 |
| R/H | rs761823581 |
-0.582 | 0.017 | N | 0.295 | 0.123 | 0.183819452728 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | I | None | 1.24419E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| R/H | rs761823581 |
-0.582 | 0.017 | N | 0.295 | 0.123 | 0.183819452728 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | I | None | 4.83E-05 | 1.3113E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs761823581 |
-0.582 | 0.017 | N | 0.295 | 0.123 | 0.183819452728 | gnomAD-4.0.0 | 1.3019E-05 | None | None | None | None | I | None | 4.00941E-05 | 6.67223E-05 | None | 0 | 2.23374E-05 | None | 0 | 0 | 1.10215E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9043 | likely_pathogenic | 0.9264 | pathogenic | 0.045 | Stabilizing | 0.209 | N | 0.481 | neutral | None | None | None | None | I |
| R/C | 0.3111 | likely_benign | 0.3708 | ambiguous | -0.172 | Destabilizing | 0.017 | N | 0.397 | neutral | N | 0.490985929 | None | None | I |
| R/D | 0.9788 | likely_pathogenic | 0.9815 | pathogenic | -0.243 | Destabilizing | 0.561 | D | 0.545 | neutral | None | None | None | None | I |
| R/E | 0.8573 | likely_pathogenic | 0.8759 | pathogenic | -0.196 | Destabilizing | 0.209 | N | 0.455 | neutral | None | None | None | None | I |
| R/F | 0.818 | likely_pathogenic | 0.8513 | pathogenic | -0.227 | Destabilizing | 0.901 | D | 0.492 | neutral | None | None | None | None | I |
| R/G | 0.8566 | likely_pathogenic | 0.8894 | pathogenic | -0.115 | Destabilizing | 0.71 | D | 0.539 | neutral | N | 0.502253329 | None | None | I |
| R/H | 0.1624 | likely_benign | 0.226 | benign | -0.59 | Destabilizing | 0.017 | N | 0.295 | neutral | N | 0.487844543 | None | None | I |
| R/I | 0.5885 | likely_pathogenic | 0.6186 | pathogenic | 0.423 | Stabilizing | 0.901 | D | 0.511 | neutral | None | None | None | None | I |
| R/K | 0.1843 | likely_benign | 0.232 | benign | -0.108 | Destabilizing | 0.002 | N | 0.248 | neutral | None | None | None | None | I |
| R/L | 0.5872 | likely_pathogenic | 0.6541 | pathogenic | 0.423 | Stabilizing | 0.503 | D | 0.533 | neutral | N | 0.51470307 | None | None | I |
| R/M | 0.671 | likely_pathogenic | 0.7473 | pathogenic | -0.006 | Destabilizing | 0.965 | D | 0.506 | neutral | None | None | None | None | I |
| R/N | 0.9136 | likely_pathogenic | 0.9318 | pathogenic | 0.047 | Stabilizing | 0.561 | D | 0.459 | neutral | None | None | None | None | I |
| R/P | 0.9912 | likely_pathogenic | 0.9912 | pathogenic | 0.316 | Stabilizing | 0.946 | D | 0.524 | neutral | N | 0.502506818 | None | None | I |
| R/Q | 0.2106 | likely_benign | 0.2732 | benign | -0.023 | Destabilizing | 0.047 | N | 0.293 | neutral | None | None | None | None | I |
| R/S | 0.9022 | likely_pathogenic | 0.9247 | pathogenic | -0.184 | Destabilizing | 0.503 | D | 0.511 | neutral | N | 0.501637772 | None | None | I |
| R/T | 0.7885 | likely_pathogenic | 0.8429 | pathogenic | -0.023 | Destabilizing | 0.561 | D | 0.539 | neutral | None | None | None | None | I |
| R/V | 0.7172 | likely_pathogenic | 0.7414 | pathogenic | 0.316 | Stabilizing | 0.561 | D | 0.551 | neutral | None | None | None | None | I |
| R/W | 0.3804 | ambiguous | 0.4561 | ambiguous | -0.362 | Destabilizing | 0.991 | D | 0.477 | neutral | None | None | None | None | I |
| R/Y | 0.5826 | likely_pathogenic | 0.6477 | pathogenic | 0.043 | Stabilizing | 0.818 | D | 0.521 | 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.