Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18504 | 55735;55736;55737 | chr2:178601487;178601486;178601485 | chr2:179466214;179466213;179466212 |
| N2AB | 16863 | 50812;50813;50814 | chr2:178601487;178601486;178601485 | chr2:179466214;179466213;179466212 |
| N2A | 15936 | 48031;48032;48033 | chr2:178601487;178601486;178601485 | chr2:179466214;179466213;179466212 |
| N2B | 9439 | 28540;28541;28542 | chr2:178601487;178601486;178601485 | chr2:179466214;179466213;179466212 |
| Novex-1 | 9564 | 28915;28916;28917 | chr2:178601487;178601486;178601485 | chr2:179466214;179466213;179466212 |
| Novex-2 | 9631 | 29116;29117;29118 | chr2:178601487;178601486;178601485 | chr2:179466214;179466213;179466212 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs778267361  |
-0.215 | 0.994 | N | 0.521 | 0.354 | 0.347217280506 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| D/G | rs778267361 |
-0.215 | 0.994 | N | 0.521 | 0.354 | 0.347217280506 | gnomAD-4.0.0 | 1.59296E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77778E-05 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | rs1254716057 |
-0.067 | 0.999 | D | 0.645 | 0.325 | 0.356281029322 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | rs1254716057 |
-0.067 | 0.999 | D | 0.645 | 0.325 | 0.356281029322 | gnomAD-4.0.0 | 6.57557E-06 | None | None | None | None | I | None | 2.41255E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1857 | likely_benign | 0.1694 | benign | 0.063 | Stabilizing | 0.989 | D | 0.511 | neutral | N | 0.446194629 | None | None | I |
| D/C | 0.7099 | likely_pathogenic | 0.6792 | pathogenic | None | Stabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | I |
| D/E | 0.1142 | likely_benign | 0.1084 | benign | -0.216 | Destabilizing | 0.751 | D | 0.239 | neutral | N | 0.410657903 | None | None | I |
| D/F | 0.7396 | likely_pathogenic | 0.7074 | pathogenic | -0.094 | Destabilizing | 0.998 | D | 0.649 | neutral | None | None | None | None | I |
| D/G | 0.2909 | likely_benign | 0.2552 | benign | -0.048 | Destabilizing | 0.994 | D | 0.521 | neutral | N | 0.433921552 | None | None | I |
| D/H | 0.4904 | ambiguous | 0.4379 | ambiguous | 0.414 | Stabilizing | 1.0 | D | 0.531 | neutral | N | 0.511496901 | None | None | I |
| D/I | 0.3532 | ambiguous | 0.338 | benign | 0.283 | Stabilizing | 0.995 | D | 0.671 | neutral | None | None | None | None | I |
| D/K | 0.4852 | ambiguous | 0.4669 | ambiguous | 0.452 | Stabilizing | 0.998 | D | 0.485 | neutral | None | None | None | None | I |
| D/L | 0.3952 | ambiguous | 0.3639 | ambiguous | 0.283 | Stabilizing | 0.46 | N | 0.421 | neutral | None | None | None | None | I |
| D/M | 0.5734 | likely_pathogenic | 0.554 | ambiguous | 0.136 | Stabilizing | 0.999 | D | 0.632 | neutral | None | None | None | None | I |
| D/N | 0.1342 | likely_benign | 0.1248 | benign | 0.351 | Stabilizing | 0.998 | D | 0.508 | neutral | N | 0.483136864 | None | None | I |
| D/P | 0.726 | likely_pathogenic | 0.7308 | pathogenic | 0.229 | Stabilizing | 1.0 | D | 0.543 | neutral | None | None | None | None | I |
| D/Q | 0.3837 | ambiguous | 0.3652 | ambiguous | 0.335 | Stabilizing | 0.998 | D | 0.536 | neutral | None | None | None | None | I |
| D/R | 0.5991 | likely_pathogenic | 0.5705 | pathogenic | 0.632 | Stabilizing | 0.998 | D | 0.606 | neutral | None | None | None | None | I |
| D/S | 0.1575 | likely_benign | 0.1452 | benign | 0.221 | Stabilizing | 0.992 | D | 0.501 | neutral | None | None | None | None | I |
| D/T | 0.2424 | likely_benign | 0.2305 | benign | 0.306 | Stabilizing | 0.999 | D | 0.49 | neutral | None | None | None | None | I |
| D/V | 0.22 | likely_benign | 0.2092 | benign | 0.229 | Stabilizing | 0.994 | D | 0.572 | neutral | N | 0.460588078 | None | None | I |
| D/W | 0.9297 | likely_pathogenic | 0.9192 | pathogenic | -0.078 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | I |
| D/Y | 0.4452 | ambiguous | 0.3887 | ambiguous | 0.128 | Stabilizing | 0.999 | D | 0.645 | neutral | D | 0.522887331 | 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.