Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16080 | 48463;48464;48465 | chr2:178616553;178616552;178616551 | chr2:179481280;179481279;179481278 |
| N2AB | 14439 | 43540;43541;43542 | chr2:178616553;178616552;178616551 | chr2:179481280;179481279;179481278 |
| N2A | 13512 | 40759;40760;40761 | chr2:178616553;178616552;178616551 | chr2:179481280;179481279;179481278 |
| N2B | 7015 | 21268;21269;21270 | chr2:178616553;178616552;178616551 | chr2:179481280;179481279;179481278 |
| Novex-1 | 7140 | 21643;21644;21645 | chr2:178616553;178616552;178616551 | chr2:179481280;179481279;179481278 |
| Novex-2 | 7207 | 21844;21845;21846 | chr2:178616553;178616552;178616551 | chr2:179481280;179481279;179481278 |
| 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 | rs775135961  |
-0.237 | 0.117 | N | 0.428 | 0.146 | 0.278143212241 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/G | rs775135961 |
-0.237 | 0.117 | N | 0.428 | 0.146 | 0.278143212241 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/G | rs775135961 |
-0.237 | 0.117 | N | 0.428 | 0.146 | 0.278143212241 | gnomAD-4.0.0 | 5.13317E-06 | None | None | None | None | N | None | 0 | 1.69739E-05 | None | 0 | 0 | None | 0 | 0 | 7.19259E-06 | 0 | 0 |
| D/N | rs1397418209 |
0.54 | 0.117 | N | 0.462 | 0.133 | 0.280181792013 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| D/N | rs1397418209 |
0.54 | 0.117 | N | 0.462 | 0.133 | 0.280181792013 | gnomAD-4.0.0 | 1.59397E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78071E-05 | 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 | 0.0922 | likely_benign | 0.109 | benign | -0.063 | Destabilizing | 0.062 | N | 0.437 | neutral | N | 0.451911324 | None | None | N |
| D/C | 0.4025 | ambiguous | 0.5222 | ambiguous | 0.099 | Stabilizing | 0.935 | D | 0.541 | neutral | None | None | None | None | N |
| D/E | 0.0904 | likely_benign | 0.1027 | benign | -0.244 | Destabilizing | None | N | 0.097 | neutral | N | 0.360642731 | None | None | N |
| D/F | 0.4465 | ambiguous | 0.5183 | ambiguous | -0.2 | Destabilizing | 0.38 | N | 0.505 | neutral | None | None | None | None | N |
| D/G | 0.1323 | likely_benign | 0.1578 | benign | -0.194 | Destabilizing | 0.117 | N | 0.428 | neutral | N | 0.468153923 | None | None | N |
| D/H | 0.19 | likely_benign | 0.2531 | benign | 0.165 | Stabilizing | 0.484 | N | 0.401 | neutral | N | 0.481788515 | None | None | N |
| D/I | 0.1699 | likely_benign | 0.2075 | benign | 0.216 | Stabilizing | 0.235 | N | 0.473 | neutral | None | None | None | None | N |
| D/K | 0.1641 | likely_benign | 0.2113 | benign | 0.463 | Stabilizing | 0.081 | N | 0.413 | neutral | None | None | None | None | N |
| D/L | 0.1845 | likely_benign | 0.2291 | benign | 0.216 | Stabilizing | 0.001 | N | 0.377 | neutral | None | None | None | None | N |
| D/M | 0.3579 | ambiguous | 0.4264 | ambiguous | 0.212 | Stabilizing | 0.698 | D | 0.49 | neutral | None | None | None | None | N |
| D/N | 0.0923 | likely_benign | 0.1035 | benign | 0.323 | Stabilizing | 0.117 | N | 0.462 | neutral | N | 0.475523577 | None | None | N |
| D/P | 0.5032 | ambiguous | 0.5432 | ambiguous | 0.143 | Stabilizing | 0.555 | D | 0.413 | neutral | None | None | None | None | N |
| D/Q | 0.1716 | likely_benign | 0.2184 | benign | 0.31 | Stabilizing | 0.235 | N | 0.399 | neutral | None | None | None | None | N |
| D/R | 0.2285 | likely_benign | 0.2912 | benign | 0.602 | Stabilizing | 0.235 | N | 0.463 | neutral | None | None | None | None | N |
| D/S | 0.0894 | likely_benign | 0.102 | benign | 0.209 | Stabilizing | 0.081 | N | 0.417 | neutral | None | None | None | None | N |
| D/T | 0.1376 | likely_benign | 0.1667 | benign | 0.307 | Stabilizing | 0.149 | N | 0.443 | neutral | None | None | None | None | N |
| D/V | 0.1013 | likely_benign | 0.1207 | benign | 0.143 | Stabilizing | 0.062 | N | 0.481 | neutral | N | 0.470093723 | None | None | N |
| D/W | 0.7671 | likely_pathogenic | 0.8218 | pathogenic | -0.155 | Destabilizing | 0.935 | D | 0.629 | neutral | None | None | None | None | N |
| D/Y | 0.1847 | likely_benign | 0.2267 | benign | 0.025 | Stabilizing | 0.484 | N | 0.501 | neutral | N | 0.482320224 | 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.