Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22499 | 67720;67721;67722 | chr2:178579702;178579701;178579700 | chr2:179444429;179444428;179444427 |
| N2AB | 20858 | 62797;62798;62799 | chr2:178579702;178579701;178579700 | chr2:179444429;179444428;179444427 |
| N2A | 19931 | 60016;60017;60018 | chr2:178579702;178579701;178579700 | chr2:179444429;179444428;179444427 |
| N2B | 13434 | 40525;40526;40527 | chr2:178579702;178579701;178579700 | chr2:179444429;179444428;179444427 |
| Novex-1 | 13559 | 40900;40901;40902 | chr2:178579702;178579701;178579700 | chr2:179444429;179444428;179444427 |
| Novex-2 | 13626 | 41101;41102;41103 | chr2:178579702;178579701;178579700 | chr2:179444429;179444428;179444427 |
| 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/G | rs574660186  |
None | 0.362 | N | 0.467 | 0.191 | 0.337135696972 | gnomAD-4.0.0 | 3.42206E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79935E-06 | 2.31895E-05 | 1.65744E-05 |
| R/Q | rs767993624 |
0.098 | 0.017 | N | 0.174 | 0.127 | None | gnomAD-2.1.1 | 3.94E-05 | None | None | None | None | N | None | 1.65371E-04 | 2.83E-05 | None | 0 | 5.16E-05 | None | 6.54E-05 | None | 0 | 2.35E-05 | 0 |
| R/Q | rs767993624 |
0.098 | 0.017 | N | 0.174 | 0.127 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs767993624 |
0.098 | 0.017 | N | 0.174 | 0.127 | None | gnomAD-4.0.0 | 1.23986E-05 | None | None | None | None | N | None | 1.20234E-04 | 1.66828E-05 | None | 0 | 2.23474E-05 | None | 0 | 1.64528E-04 | 3.39128E-06 | 4.39194E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3666 | ambiguous | 0.3536 | ambiguous | -0.739 | Destabilizing | 0.061 | N | 0.351 | neutral | None | None | None | None | N |
| R/C | 0.1979 | likely_benign | 0.1821 | benign | -0.712 | Destabilizing | 0.983 | D | 0.488 | neutral | None | None | None | None | N |
| R/D | 0.7322 | likely_pathogenic | 0.7149 | pathogenic | -0.157 | Destabilizing | 0.129 | N | 0.437 | neutral | None | None | None | None | N |
| R/E | 0.3394 | likely_benign | 0.3441 | ambiguous | -0.034 | Destabilizing | None | N | 0.175 | neutral | None | None | None | None | N |
| R/F | 0.7688 | likely_pathogenic | 0.7373 | pathogenic | -0.573 | Destabilizing | 0.716 | D | 0.545 | neutral | None | None | None | None | N |
| R/G | 0.3427 | ambiguous | 0.3199 | benign | -1.05 | Destabilizing | 0.362 | N | 0.467 | neutral | N | 0.48590781 | None | None | N |
| R/H | 0.1284 | likely_benign | 0.1147 | benign | -1.4 | Destabilizing | 0.716 | D | 0.443 | neutral | None | None | None | None | N |
| R/I | 0.3429 | ambiguous | 0.3214 | benign | 0.097 | Stabilizing | 0.264 | N | 0.525 | neutral | None | None | None | None | N |
| R/K | 0.1219 | likely_benign | 0.1108 | benign | -0.888 | Destabilizing | 0.061 | N | 0.194 | neutral | None | None | None | None | N |
| R/L | 0.3603 | ambiguous | 0.3391 | benign | 0.097 | Stabilizing | 0.002 | N | 0.237 | neutral | N | 0.464801819 | None | None | N |
| R/M | 0.3599 | ambiguous | 0.3354 | benign | -0.244 | Destabilizing | 0.716 | D | 0.495 | neutral | None | None | None | None | N |
| R/N | 0.5525 | ambiguous | 0.5514 | ambiguous | -0.371 | Destabilizing | 0.418 | N | 0.335 | neutral | None | None | None | None | N |
| R/P | 0.3588 | ambiguous | 0.3705 | ambiguous | -0.161 | Destabilizing | 0.736 | D | 0.547 | neutral | N | 0.432766759 | None | None | N |
| R/Q | 0.1191 | likely_benign | 0.1132 | benign | -0.506 | Destabilizing | 0.017 | N | 0.174 | neutral | N | 0.45927857 | None | None | N |
| R/S | 0.4837 | ambiguous | 0.4785 | ambiguous | -1.068 | Destabilizing | 0.129 | N | 0.456 | neutral | None | None | None | None | N |
| R/T | 0.1832 | likely_benign | 0.1893 | benign | -0.765 | Destabilizing | 0.228 | N | 0.475 | neutral | None | None | None | None | N |
| R/V | 0.3659 | ambiguous | 0.353 | ambiguous | -0.161 | Destabilizing | 0.129 | N | 0.465 | neutral | None | None | None | None | N |
| R/W | 0.3866 | ambiguous | 0.3323 | benign | -0.26 | Destabilizing | 0.983 | D | 0.495 | neutral | None | None | None | None | N |
| R/Y | 0.6024 | likely_pathogenic | 0.5653 | pathogenic | 0.03 | Stabilizing | 0.836 | D | 0.558 | 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.