Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21672 | 65239;65240;65241 | chr2:178584537;178584536;178584535 | chr2:179449264;179449263;179449262 |
| N2AB | 20031 | 60316;60317;60318 | chr2:178584537;178584536;178584535 | chr2:179449264;179449263;179449262 |
| N2A | 19104 | 57535;57536;57537 | chr2:178584537;178584536;178584535 | chr2:179449264;179449263;179449262 |
| N2B | 12607 | 38044;38045;38046 | chr2:178584537;178584536;178584535 | chr2:179449264;179449263;179449262 |
| Novex-1 | 12732 | 38419;38420;38421 | chr2:178584537;178584536;178584535 | chr2:179449264;179449263;179449262 |
| Novex-2 | 12799 | 38620;38621;38622 | chr2:178584537;178584536;178584535 | chr2:179449264;179449263;179449262 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/K | rs1452681242  |
-0.231 | 0.684 | N | 0.291 | 0.238 | 0.194818534648 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| N/K | rs1452681242 |
-0.231 | 0.684 | N | 0.291 | 0.238 | 0.194818534648 | gnomAD-4.0.0 | 2.73835E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59932E-06 | 0 | 0 |
| N/S | None | None | 0.078 | N | 0.097 | 0.101 | 0.132336055621 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 3.66327E-05 |
| N/Y | None | None | 0.792 | N | 0.455 | 0.285 | 0.338834610459 | gnomAD-4.0.0 | 1.5935E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43435E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3212 | likely_benign | 0.3328 | benign | -0.799 | Destabilizing | 0.373 | N | 0.366 | neutral | None | None | None | None | N |
| N/C | 0.328 | likely_benign | 0.3203 | benign | -0.079 | Destabilizing | 0.996 | D | 0.41 | neutral | None | None | None | None | N |
| N/D | 0.2396 | likely_benign | 0.2735 | benign | -1.327 | Destabilizing | 0.684 | D | 0.299 | neutral | N | 0.463167024 | None | None | N |
| N/E | 0.5881 | likely_pathogenic | 0.6469 | pathogenic | -1.135 | Destabilizing | 0.742 | D | 0.285 | neutral | None | None | None | None | N |
| N/F | 0.5573 | ambiguous | 0.5956 | pathogenic | -0.224 | Destabilizing | 0.009 | N | 0.311 | neutral | None | None | None | None | N |
| N/G | 0.284 | likely_benign | 0.2908 | benign | -1.213 | Destabilizing | 0.004 | N | 0.065 | neutral | None | None | None | None | N |
| N/H | 0.1292 | likely_benign | 0.1427 | benign | -0.985 | Destabilizing | 0.979 | D | 0.355 | neutral | N | 0.479656629 | None | None | N |
| N/I | 0.4698 | ambiguous | 0.5109 | ambiguous | 0.296 | Stabilizing | 0.884 | D | 0.495 | neutral | N | 0.472511328 | None | None | N |
| N/K | 0.5128 | ambiguous | 0.5726 | pathogenic | -0.511 | Destabilizing | 0.684 | D | 0.291 | neutral | N | 0.490737627 | None | None | N |
| N/L | 0.3271 | likely_benign | 0.3581 | ambiguous | 0.296 | Stabilizing | 0.59 | D | 0.403 | neutral | None | None | None | None | N |
| N/M | 0.4277 | ambiguous | 0.4587 | ambiguous | 0.634 | Stabilizing | 0.984 | D | 0.383 | neutral | None | None | None | None | N |
| N/P | 0.9221 | likely_pathogenic | 0.9221 | pathogenic | -0.039 | Destabilizing | 0.953 | D | 0.447 | neutral | None | None | None | None | N |
| N/Q | 0.4246 | ambiguous | 0.4597 | ambiguous | -0.969 | Destabilizing | 0.953 | D | 0.351 | neutral | None | None | None | None | N |
| N/R | 0.4745 | ambiguous | 0.5212 | ambiguous | -0.817 | Destabilizing | 0.91 | D | 0.371 | neutral | None | None | None | None | N |
| N/S | 0.0798 | likely_benign | 0.0786 | benign | -1.247 | Destabilizing | 0.078 | N | 0.097 | neutral | N | 0.421778974 | None | None | N |
| N/T | 0.1406 | likely_benign | 0.148 | benign | -0.868 | Destabilizing | 0.007 | N | 0.11 | neutral | N | 0.394090941 | None | None | N |
| N/V | 0.4211 | ambiguous | 0.4517 | ambiguous | -0.039 | Destabilizing | 0.59 | D | 0.442 | neutral | None | None | None | None | N |
| N/W | 0.7907 | likely_pathogenic | 0.8072 | pathogenic | -0.154 | Destabilizing | 0.996 | D | 0.429 | neutral | None | None | None | None | N |
| N/Y | 0.2091 | likely_benign | 0.2437 | benign | 0.135 | Stabilizing | 0.792 | D | 0.455 | neutral | N | 0.519001664 | 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.