Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16646 | 50161;50162;50163 | chr2:178612785;178612784;178612783 | chr2:179477512;179477511;179477510 |
| N2AB | 15005 | 45238;45239;45240 | chr2:178612785;178612784;178612783 | chr2:179477512;179477511;179477510 |
| N2A | 14078 | 42457;42458;42459 | chr2:178612785;178612784;178612783 | chr2:179477512;179477511;179477510 |
| N2B | 7581 | 22966;22967;22968 | chr2:178612785;178612784;178612783 | chr2:179477512;179477511;179477510 |
| Novex-1 | 7706 | 23341;23342;23343 | chr2:178612785;178612784;178612783 | chr2:179477512;179477511;179477510 |
| Novex-2 | 7773 | 23542;23543;23544 | chr2:178612785;178612784;178612783 | chr2:179477512;179477511;179477510 |
| 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/Q | rs746384579  |
0.145 | 0.614 | N | 0.338 | 0.175 | 0.126345400529 | gnomAD-2.1.1 | 7.28E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.24E-05 | None | 1.67999E-04 | None | 0 | 1.11572E-04 | 0 |
| R/Q | rs746384579 |
0.145 | 0.614 | N | 0.338 | 0.175 | 0.126345400529 | gnomAD-3.1.2 | 5.93E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.03087E-04 | 0 | 0 |
| R/Q | rs746384579 |
0.145 | 0.614 | N | 0.338 | 0.175 | 0.126345400529 | gnomAD-4.0.0 | 3.85265E-05 | None | None | None | None | N | None | 2.67895E-05 | 1.68828E-05 | None | 0 | 4.49438E-05 | None | 0 | 0 | 3.98937E-05 | 8.86761E-05 | 3.21337E-05 |
| R/W | rs794729448 |
-0.334 | 0.996 | N | 0.411 | 0.311 | 0.31077124679 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| R/W | rs794729448 |
-0.334 | 0.996 | N | 0.411 | 0.311 | 0.31077124679 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.46E-05 | 0 | 0 | 2.07814E-04 | 0 |
| R/W | rs794729448 |
-0.334 | 0.996 | N | 0.411 | 0.311 | 0.31077124679 | gnomAD-4.0.0 | 4.97106E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.13156E-05 | 0 | 4.24393E-06 | 0 | 1.60601E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5639 | ambiguous | 0.6985 | pathogenic | -0.152 | Destabilizing | 0.134 | N | 0.367 | neutral | None | None | None | None | N |
| R/C | 0.3583 | ambiguous | 0.4107 | ambiguous | -0.299 | Destabilizing | 0.984 | D | 0.378 | neutral | None | None | None | None | N |
| R/D | 0.8551 | likely_pathogenic | 0.9071 | pathogenic | 0.024 | Stabilizing | 0.428 | N | 0.462 | neutral | None | None | None | None | N |
| R/E | 0.465 | ambiguous | 0.5862 | pathogenic | 0.111 | Stabilizing | 0.134 | N | 0.281 | neutral | None | None | None | None | N |
| R/F | 0.7841 | likely_pathogenic | 0.8461 | pathogenic | -0.249 | Destabilizing | 0.942 | D | 0.455 | neutral | None | None | None | None | N |
| R/G | 0.4128 | ambiguous | 0.5655 | pathogenic | -0.386 | Destabilizing | 0.589 | D | 0.439 | neutral | N | 0.454645444 | None | None | N |
| R/H | 0.1788 | likely_benign | 0.2085 | benign | -0.811 | Destabilizing | 0.842 | D | 0.261 | neutral | None | None | None | None | N |
| R/I | 0.4502 | ambiguous | 0.5701 | pathogenic | 0.441 | Stabilizing | 0.842 | D | 0.509 | neutral | None | None | None | None | N |
| R/K | 0.0972 | likely_benign | 0.1002 | benign | -0.198 | Destabilizing | None | N | 0.089 | neutral | None | None | None | None | N |
| R/L | 0.4054 | ambiguous | 0.5158 | ambiguous | 0.441 | Stabilizing | 0.589 | D | 0.439 | neutral | N | 0.454938596 | None | None | N |
| R/M | 0.4497 | ambiguous | 0.5791 | pathogenic | -0.029 | Destabilizing | 0.942 | D | 0.347 | neutral | None | None | None | None | N |
| R/N | 0.7728 | likely_pathogenic | 0.8397 | pathogenic | 0.072 | Stabilizing | 0.428 | N | 0.298 | neutral | None | None | None | None | N |
| R/P | 0.8968 | likely_pathogenic | 0.9299 | pathogenic | 0.265 | Stabilizing | 0.744 | D | 0.489 | neutral | N | 0.449023707 | None | None | N |
| R/Q | 0.1301 | likely_benign | 0.151 | benign | -0.031 | Destabilizing | 0.614 | D | 0.338 | neutral | N | 0.426713261 | None | None | N |
| R/S | 0.6356 | likely_pathogenic | 0.7605 | pathogenic | -0.398 | Destabilizing | 0.134 | N | 0.357 | neutral | None | None | None | None | N |
| R/T | 0.3441 | ambiguous | 0.4888 | ambiguous | -0.157 | Destabilizing | 0.428 | N | 0.393 | neutral | None | None | None | None | N |
| R/V | 0.4933 | ambiguous | 0.59 | pathogenic | 0.265 | Stabilizing | 0.428 | N | 0.513 | neutral | None | None | None | None | N |
| R/W | 0.3943 | ambiguous | 0.4905 | ambiguous | -0.196 | Destabilizing | 0.996 | D | 0.411 | neutral | N | 0.513261014 | None | None | N |
| R/Y | 0.6872 | likely_pathogenic | 0.7527 | pathogenic | 0.187 | Stabilizing | 0.942 | D | 0.54 | 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.