Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16682 | 50269;50270;50271 | chr2:178612481;178612480;178612479 | chr2:179477208;179477207;179477206 |
| N2AB | 15041 | 45346;45347;45348 | chr2:178612481;178612480;178612479 | chr2:179477208;179477207;179477206 |
| N2A | 14114 | 42565;42566;42567 | chr2:178612481;178612480;178612479 | chr2:179477208;179477207;179477206 |
| N2B | 7617 | 23074;23075;23076 | chr2:178612481;178612480;178612479 | chr2:179477208;179477207;179477206 |
| Novex-1 | 7742 | 23449;23450;23451 | chr2:178612481;178612480;178612479 | chr2:179477208;179477207;179477206 |
| Novex-2 | 7809 | 23650;23651;23652 | chr2:178612481;178612480;178612479 | chr2:179477208;179477207;179477206 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs1349579168  |
0.006 | 0.997 | D | 0.636 | 0.502 | 0.717612795731 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.69E-05 | None | 0 | None | 0 | 0 | 0 |
| P/L | rs1349579168 |
0.006 | 0.997 | D | 0.636 | 0.502 | 0.717612795731 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.94856E-04 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | rs1349579168 |
0.006 | 0.997 | D | 0.636 | 0.502 | 0.717612795731 | gnomAD-4.0.0 | 1.24064E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.24467E-05 | None | 0 | 0 | 0 | 1.09856E-05 | 0 |
| P/S | None | None | 0.978 | D | 0.581 | 0.41 | 0.298056030225 | gnomAD-4.0.0 | 4.78432E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.58797E-06 | 0 | 0 |
| P/T | rs1231714517 |
-0.033 | 0.997 | D | 0.573 | 0.427 | 0.461759001683 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.11E-06 | 0 |
| P/T | rs1231714517 |
-0.033 | 0.997 | D | 0.573 | 0.427 | 0.461759001683 | gnomAD-4.0.0 | 1.59477E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86266E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1284 | likely_benign | 0.1475 | benign | -0.298 | Destabilizing | 0.543 | D | 0.384 | neutral | D | 0.533542512 | None | None | I |
| P/C | 0.8272 | likely_pathogenic | 0.8598 | pathogenic | -0.499 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| P/D | 0.6479 | likely_pathogenic | 0.7802 | pathogenic | -0.161 | Destabilizing | 0.999 | D | 0.63 | neutral | None | None | None | None | I |
| P/E | 0.4103 | ambiguous | 0.5362 | ambiguous | -0.293 | Destabilizing | 0.998 | D | 0.564 | neutral | None | None | None | None | I |
| P/F | 0.8042 | likely_pathogenic | 0.8536 | pathogenic | -0.701 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | I |
| P/G | 0.5703 | likely_pathogenic | 0.6315 | pathogenic | -0.396 | Destabilizing | 0.992 | D | 0.585 | neutral | None | None | None | None | I |
| P/H | 0.3756 | ambiguous | 0.4775 | ambiguous | -0.077 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | D | 0.614168327 | None | None | I |
| P/I | 0.5425 | ambiguous | 0.6092 | pathogenic | -0.2 | Destabilizing | 0.999 | D | 0.745 | deleterious | None | None | None | None | I |
| P/K | 0.3393 | likely_benign | 0.4819 | ambiguous | -0.172 | Destabilizing | 0.983 | D | 0.58 | neutral | None | None | None | None | I |
| P/L | 0.2451 | likely_benign | 0.3022 | benign | -0.2 | Destabilizing | 0.997 | D | 0.636 | neutral | D | 0.646393702 | None | None | I |
| P/M | 0.5655 | likely_pathogenic | 0.6182 | pathogenic | -0.172 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| P/N | 0.571 | likely_pathogenic | 0.6489 | pathogenic | 0.095 | Stabilizing | 0.999 | D | 0.715 | prob.delet. | None | None | None | None | I |
| P/Q | 0.2425 | likely_benign | 0.3038 | benign | -0.179 | Destabilizing | 0.998 | D | 0.65 | neutral | None | None | None | None | I |
| P/R | 0.2278 | likely_benign | 0.3392 | benign | 0.31 | Stabilizing | 0.391 | N | 0.461 | neutral | D | 0.571493962 | None | None | I |
| P/S | 0.2524 | likely_benign | 0.3168 | benign | -0.247 | Destabilizing | 0.978 | D | 0.581 | neutral | D | 0.578945416 | None | None | I |
| P/T | 0.2061 | likely_benign | 0.2607 | benign | -0.28 | Destabilizing | 0.997 | D | 0.573 | neutral | D | 0.585832256 | None | None | I |
| P/V | 0.3615 | ambiguous | 0.4075 | ambiguous | -0.199 | Destabilizing | 0.998 | D | 0.589 | neutral | None | None | None | None | I |
| P/W | 0.9109 | likely_pathogenic | 0.944 | pathogenic | -0.775 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| P/Y | 0.7729 | likely_pathogenic | 0.8367 | pathogenic | -0.441 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | 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.