Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26866 | 80821;80822;80823 | chr2:178565536;178565535;178565534 | chr2:179430263;179430262;179430261 |
| N2AB | 25225 | 75898;75899;75900 | chr2:178565536;178565535;178565534 | chr2:179430263;179430262;179430261 |
| N2A | 24298 | 73117;73118;73119 | chr2:178565536;178565535;178565534 | chr2:179430263;179430262;179430261 |
| N2B | 17801 | 53626;53627;53628 | chr2:178565536;178565535;178565534 | chr2:179430263;179430262;179430261 |
| Novex-1 | 17926 | 54001;54002;54003 | chr2:178565536;178565535;178565534 | chr2:179430263;179430262;179430261 |
| Novex-2 | 17993 | 54202;54203;54204 | chr2:178565536;178565535;178565534 | chr2:179430263;179430262;179430261 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/E | None | None | 0.049 | N | 0.403 | 0.248 | 0.335661160332 | gnomAD-4.0.0 | 1.59174E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43291E-05 | 0 |
| V/L | rs747456605  |
None | None | N | 0.223 | 0.07 | 0.236890367714 | gnomAD-4.0.0 | 6.84291E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99572E-07 | 0 | 0 |
| V/M | rs747456605 |
-0.287 | 0.468 | N | 0.381 | 0.044 | 0.315314060047 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.77E-05 | 0 |
| V/M | rs747456605 |
-0.287 | 0.468 | N | 0.381 | 0.044 | 0.315314060047 | gnomAD-4.0.0 | 7.5272E-06 | None | None | None | None | N | None | 0 | 2.23634E-05 | None | 0 | 0 | None | 0 | 0 | 8.99572E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1154 | likely_benign | 0.1008 | benign | -1.273 | Destabilizing | None | N | 0.128 | neutral | N | 0.418997746 | None | None | N |
| V/C | 0.6058 | likely_pathogenic | 0.5815 | pathogenic | -0.795 | Destabilizing | 0.703 | D | 0.407 | neutral | None | None | None | None | N |
| V/D | 0.2028 | likely_benign | 0.1768 | benign | -1.093 | Destabilizing | 0.25 | N | 0.547 | neutral | None | None | None | None | N |
| V/E | 0.1669 | likely_benign | 0.1571 | benign | -1.062 | Destabilizing | 0.049 | N | 0.403 | neutral | N | 0.365568693 | None | None | N |
| V/F | 0.1289 | likely_benign | 0.1126 | benign | -0.843 | Destabilizing | 0.369 | N | 0.569 | neutral | None | None | None | None | N |
| V/G | 0.15 | likely_benign | 0.1329 | benign | -1.604 | Destabilizing | 0.049 | N | 0.371 | neutral | N | 0.449648727 | None | None | N |
| V/H | 0.4124 | ambiguous | 0.3791 | ambiguous | -1.084 | Destabilizing | 0.703 | D | 0.493 | neutral | None | None | None | None | N |
| V/I | 0.0679 | likely_benign | 0.0668 | benign | -0.458 | Destabilizing | None | N | 0.184 | neutral | None | None | None | None | N |
| V/K | 0.3109 | likely_benign | 0.2813 | benign | -1.103 | Destabilizing | 0.064 | N | 0.433 | neutral | None | None | None | None | N |
| V/L | 0.1112 | likely_benign | 0.0987 | benign | -0.458 | Destabilizing | None | N | 0.223 | neutral | N | 0.430830893 | None | None | N |
| V/M | 0.1045 | likely_benign | 0.0945 | benign | -0.414 | Destabilizing | 0.468 | N | 0.381 | neutral | N | 0.440933243 | None | None | N |
| V/N | 0.1476 | likely_benign | 0.1319 | benign | -0.981 | Destabilizing | 0.25 | N | 0.581 | neutral | None | None | None | None | N |
| V/P | 0.1998 | likely_benign | 0.1608 | benign | -0.695 | Destabilizing | None | N | 0.387 | neutral | None | None | None | None | N |
| V/Q | 0.2149 | likely_benign | 0.2029 | benign | -1.092 | Destabilizing | 0.013 | N | 0.427 | neutral | None | None | None | None | N |
| V/R | 0.3368 | likely_benign | 0.3034 | benign | -0.629 | Destabilizing | 0.25 | N | 0.578 | neutral | None | None | None | None | N |
| V/S | 0.1219 | likely_benign | 0.1121 | benign | -1.489 | Destabilizing | 0.005 | N | 0.397 | neutral | None | None | None | None | N |
| V/T | 0.1288 | likely_benign | 0.1182 | benign | -1.346 | Destabilizing | 0.064 | N | 0.287 | neutral | None | None | None | None | N |
| V/W | 0.6939 | likely_pathogenic | 0.6495 | pathogenic | -1.082 | Destabilizing | 0.964 | D | 0.541 | neutral | None | None | None | None | N |
| V/Y | 0.3911 | ambiguous | 0.3566 | ambiguous | -0.755 | Destabilizing | 0.703 | D | 0.554 | 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.