Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29623 | 89092;89093;89094 | chr2:178554480;178554479;178554478 | chr2:179419207;179419206;179419205 |
| N2AB | 27982 | 84169;84170;84171 | chr2:178554480;178554479;178554478 | chr2:179419207;179419206;179419205 |
| N2A | 27055 | 81388;81389;81390 | chr2:178554480;178554479;178554478 | chr2:179419207;179419206;179419205 |
| N2B | 20558 | 61897;61898;61899 | chr2:178554480;178554479;178554478 | chr2:179419207;179419206;179419205 |
| Novex-1 | 20683 | 62272;62273;62274 | chr2:178554480;178554479;178554478 | chr2:179419207;179419206;179419205 |
| Novex-2 | 20750 | 62473;62474;62475 | chr2:178554480;178554479;178554478 | chr2:179419207;179419206;179419205 |
| 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/E | rs753493628  |
0.027 | None | N | 0.097 | 0.045 | 0.0482279557977 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| D/E | rs753493628 |
0.027 | None | N | 0.097 | 0.045 | 0.0482279557977 | gnomAD-4.0.0 | 4.77591E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.57604E-06 | 0 | 0 |
| D/G | None | None | None | N | 0.131 | 0.169 | 0.168933306366 | gnomAD-4.0.0 | 1.59197E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.41313E-04 | 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 | 0.0822 | likely_benign | 0.0795 | benign | -0.17 | Destabilizing | None | N | 0.169 | neutral | N | 0.469452704 | None | None | N |
| D/C | 0.3371 | likely_benign | 0.3391 | benign | -0.141 | Destabilizing | 0.747 | D | 0.272 | neutral | None | None | None | None | N |
| D/E | 0.0818 | likely_benign | 0.0755 | benign | -0.186 | Destabilizing | None | N | 0.097 | neutral | N | 0.352684248 | None | None | N |
| D/F | 0.3639 | ambiguous | 0.3802 | ambiguous | 0.092 | Stabilizing | 0.112 | N | 0.385 | neutral | None | None | None | None | N |
| D/G | 0.1012 | likely_benign | 0.1015 | benign | -0.364 | Destabilizing | None | N | 0.131 | neutral | N | 0.462393446 | None | None | N |
| D/H | 0.1558 | likely_benign | 0.1622 | benign | 0.504 | Stabilizing | None | N | 0.171 | neutral | N | 0.483379745 | None | None | N |
| D/I | 0.1553 | likely_benign | 0.1554 | benign | 0.298 | Stabilizing | 0.112 | N | 0.478 | neutral | None | None | None | None | N |
| D/K | 0.1474 | likely_benign | 0.1415 | benign | 0.448 | Stabilizing | 0.007 | N | 0.221 | neutral | None | None | None | None | N |
| D/L | 0.19 | likely_benign | 0.1861 | benign | 0.298 | Stabilizing | 0.035 | N | 0.413 | neutral | None | None | None | None | N |
| D/M | 0.3209 | likely_benign | 0.3147 | benign | 0.216 | Stabilizing | 0.439 | N | 0.305 | neutral | None | None | None | None | N |
| D/N | 0.0751 | likely_benign | 0.0746 | benign | -0.07 | Destabilizing | 0.006 | N | 0.176 | neutral | N | 0.483326078 | None | None | N |
| D/P | 0.2562 | likely_benign | 0.235 | benign | 0.164 | Stabilizing | 0.068 | N | 0.362 | neutral | None | None | None | None | N |
| D/Q | 0.1403 | likely_benign | 0.1358 | benign | 0.006 | Stabilizing | 0.001 | N | 0.145 | neutral | None | None | None | None | N |
| D/R | 0.1827 | likely_benign | 0.1852 | benign | 0.717 | Stabilizing | 0.018 | N | 0.442 | neutral | None | None | None | None | N |
| D/S | 0.0773 | likely_benign | 0.0759 | benign | -0.144 | Destabilizing | 0.007 | N | 0.127 | neutral | None | None | None | None | N |
| D/T | 0.1107 | likely_benign | 0.1049 | benign | 0.03 | Stabilizing | 0.015 | N | 0.286 | neutral | None | None | None | None | N |
| D/V | 0.1004 | likely_benign | 0.0998 | benign | 0.164 | Stabilizing | 0.013 | N | 0.415 | neutral | N | 0.494369791 | None | None | N |
| D/W | 0.7584 | likely_pathogenic | 0.7666 | pathogenic | 0.267 | Stabilizing | 0.747 | D | 0.279 | neutral | None | None | None | None | N |
| D/Y | 0.1617 | likely_benign | 0.1721 | benign | 0.352 | Stabilizing | 0.046 | N | 0.466 | neutral | N | 0.483633235 | 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.