Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2890 | 8893;8894;8895 | chr2:178769913;178769912;178769911 | chr2:179634640;179634639;179634638 |
| N2AB | 2890 | 8893;8894;8895 | chr2:178769913;178769912;178769911 | chr2:179634640;179634639;179634638 |
| N2A | 2890 | 8893;8894;8895 | chr2:178769913;178769912;178769911 | chr2:179634640;179634639;179634638 |
| N2B | 2844 | 8755;8756;8757 | chr2:178769913;178769912;178769911 | chr2:179634640;179634639;179634638 |
| Novex-1 | 2844 | 8755;8756;8757 | chr2:178769913;178769912;178769911 | chr2:179634640;179634639;179634638 |
| Novex-2 | 2844 | 8755;8756;8757 | chr2:178769913;178769912;178769911 | chr2:179634640;179634639;179634638 |
| Novex-3 | 2890 | 8893;8894;8895 | chr2:178769913;178769912;178769911 | chr2:179634640;179634639;179634638 |
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/D | rs767589357  |
0.553 | None | N | 0.104 | 0.162 | 0.223847106136 | gnomAD-2.1.1 | 2.39E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.3E-05 | 0 |
| N/D | rs767589357 |
0.553 | None | N | 0.104 | 0.162 | 0.223847106136 | gnomAD-4.0.0 | 1.7496E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.14217E-05 | 0 | 0 |
| N/S | rs1574561545 |
None | None | N | 0.089 | 0.159 | 0.0297737177859 | gnomAD-4.0.0 | 1.36816E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7986E-06 | 0 | 0 |
| N/T | None | None | 0.027 | D | 0.249 | 0.245 | 0.128392430309 | gnomAD-4.0.0 | 6.84082E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99298E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.1708 | likely_benign | 0.1904 | benign | -0.433 | Destabilizing | 0.035 | N | 0.311 | neutral | None | None | None | None | N |
| N/C | 0.2387 | likely_benign | 0.3073 | benign | 0.244 | Stabilizing | 0.824 | D | 0.429 | neutral | None | None | None | None | N |
| N/D | 0.0805 | likely_benign | 0.0824 | benign | 0.223 | Stabilizing | None | N | 0.104 | neutral | N | 0.438157617 | None | None | N |
| N/E | 0.3236 | likely_benign | 0.3901 | ambiguous | 0.211 | Stabilizing | 0.035 | N | 0.257 | neutral | None | None | None | None | N |
| N/F | 0.6253 | likely_pathogenic | 0.6986 | pathogenic | -0.747 | Destabilizing | 0.555 | D | 0.432 | neutral | None | None | None | None | N |
| N/G | 0.1661 | likely_benign | 0.1789 | benign | -0.63 | Destabilizing | 0.035 | N | 0.293 | neutral | None | None | None | None | N |
| N/H | 0.1428 | likely_benign | 0.1683 | benign | -0.569 | Destabilizing | 0.484 | N | 0.364 | neutral | D | 0.613547043 | None | None | N |
| N/I | 0.305 | likely_benign | 0.3773 | ambiguous | 0.004 | Stabilizing | 0.317 | N | 0.433 | neutral | D | 0.636551735 | None | None | N |
| N/K | 0.3044 | likely_benign | 0.4018 | ambiguous | 0.123 | Stabilizing | 0.062 | N | 0.246 | neutral | D | 0.635226779 | None | None | N |
| N/L | 0.3145 | likely_benign | 0.3849 | ambiguous | 0.004 | Stabilizing | 0.149 | N | 0.406 | neutral | None | None | None | None | N |
| N/M | 0.3315 | likely_benign | 0.3926 | ambiguous | 0.258 | Stabilizing | 0.935 | D | 0.409 | neutral | None | None | None | None | N |
| N/P | 0.2691 | likely_benign | 0.3296 | benign | -0.114 | Destabilizing | 0.38 | N | 0.404 | neutral | None | None | None | None | N |
| N/Q | 0.3431 | ambiguous | 0.4101 | ambiguous | -0.368 | Destabilizing | 0.38 | N | 0.319 | neutral | None | None | None | None | N |
| N/R | 0.36 | ambiguous | 0.4737 | ambiguous | 0.161 | Stabilizing | 0.38 | N | 0.321 | neutral | None | None | None | None | N |
| N/S | 0.06 | likely_benign | 0.059 | benign | -0.22 | Destabilizing | None | N | 0.089 | neutral | N | 0.498486811 | None | None | N |
| N/T | 0.0948 | likely_benign | 0.1054 | benign | -0.07 | Destabilizing | 0.027 | N | 0.249 | neutral | D | 0.580405861 | None | None | N |
| N/V | 0.3 | likely_benign | 0.3609 | ambiguous | -0.114 | Destabilizing | 0.38 | N | 0.417 | neutral | None | None | None | None | N |
| N/W | 0.7634 | likely_pathogenic | 0.8334 | pathogenic | -0.697 | Destabilizing | 0.935 | D | 0.555 | neutral | None | None | None | None | N |
| N/Y | 0.2311 | likely_benign | 0.2891 | benign | -0.431 | Destabilizing | 0.484 | N | 0.426 | neutral | D | 0.549153015 | 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.