Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28410 | 85453;85454;85455 | chr2:178560904;178560903;178560902 | chr2:179425631;179425630;179425629 |
| N2AB | 26769 | 80530;80531;80532 | chr2:178560904;178560903;178560902 | chr2:179425631;179425630;179425629 |
| N2A | 25842 | 77749;77750;77751 | chr2:178560904;178560903;178560902 | chr2:179425631;179425630;179425629 |
| N2B | 19345 | 58258;58259;58260 | chr2:178560904;178560903;178560902 | chr2:179425631;179425630;179425629 |
| Novex-1 | 19470 | 58633;58634;58635 | chr2:178560904;178560903;178560902 | chr2:179425631;179425630;179425629 |
| Novex-2 | 19537 | 58834;58835;58836 | chr2:178560904;178560903;178560902 | chr2:179425631;179425630;179425629 |
| 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 | rs762042364  |
-0.147 | 0.472 | N | 0.209 | 0.089 | 0.112648838833 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| D/E | rs762042364 |
-0.147 | 0.472 | N | 0.209 | 0.089 | 0.112648838833 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/E | rs762042364 |
-0.147 | 0.472 | N | 0.209 | 0.089 | 0.112648838833 | gnomAD-4.0.0 | 6.40635E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.19645E-05 | 0 | 0 |
| D/N | None | None | 0.012 | N | 0.099 | 0.156 | 0.0954503805726 | gnomAD-4.0.0 | 1.59153E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02462E-05 |
| D/V | rs1425562025 |
0.264 | 0.521 | N | 0.313 | 0.244 | 0.42130639912 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 1.14732E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/V | rs1425562025 |
0.264 | 0.521 | N | 0.313 | 0.244 | 0.42130639912 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/V | rs1425562025 |
0.264 | 0.521 | N | 0.313 | 0.244 | 0.42130639912 | gnomAD-4.0.0 | 6.5697E-06 | None | None | None | None | N | None | 2.41138E-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 | 0.121 | likely_benign | 0.1304 | benign | -0.04 | Destabilizing | 0.007 | N | 0.215 | neutral | N | 0.458681082 | None | None | N |
| D/C | 0.5493 | ambiguous | 0.5833 | pathogenic | 0.043 | Stabilizing | 0.987 | D | 0.323 | neutral | None | None | None | None | N |
| D/E | 0.1191 | likely_benign | 0.123 | benign | -0.236 | Destabilizing | 0.472 | N | 0.209 | neutral | N | 0.484760512 | None | None | N |
| D/F | 0.5394 | ambiguous | 0.56 | ambiguous | -0.092 | Destabilizing | 0.91 | D | 0.339 | neutral | None | None | None | None | N |
| D/G | 0.1268 | likely_benign | 0.1292 | benign | -0.181 | Destabilizing | 0.309 | N | 0.273 | neutral | N | 0.442505671 | None | None | N |
| D/H | 0.2696 | likely_benign | 0.2899 | benign | 0.339 | Stabilizing | 0.939 | D | 0.277 | neutral | N | 0.470797856 | None | None | N |
| D/I | 0.2716 | likely_benign | 0.2904 | benign | 0.269 | Stabilizing | 0.59 | D | 0.349 | neutral | None | None | None | None | N |
| D/K | 0.255 | likely_benign | 0.2852 | benign | 0.505 | Stabilizing | 0.742 | D | 0.273 | neutral | None | None | None | None | N |
| D/L | 0.3064 | likely_benign | 0.3378 | benign | 0.269 | Stabilizing | 0.009 | N | 0.257 | neutral | None | None | None | None | N |
| D/M | 0.5106 | ambiguous | 0.5247 | ambiguous | 0.207 | Stabilizing | 0.91 | D | 0.313 | neutral | None | None | None | None | N |
| D/N | 0.101 | likely_benign | 0.1012 | benign | 0.251 | Stabilizing | 0.012 | N | 0.099 | neutral | N | 0.473524798 | None | None | N |
| D/P | 0.3789 | ambiguous | 0.4104 | ambiguous | 0.187 | Stabilizing | 0.953 | D | 0.325 | neutral | None | None | None | None | N |
| D/Q | 0.2491 | likely_benign | 0.2671 | benign | 0.263 | Stabilizing | 0.953 | D | 0.274 | neutral | None | None | None | None | N |
| D/R | 0.2976 | likely_benign | 0.3226 | benign | 0.686 | Stabilizing | 0.953 | D | 0.337 | neutral | None | None | None | None | N |
| D/S | 0.1088 | likely_benign | 0.1115 | benign | 0.159 | Stabilizing | 0.101 | N | 0.139 | neutral | None | None | None | None | N |
| D/T | 0.1868 | likely_benign | 0.1995 | benign | 0.273 | Stabilizing | 0.59 | D | 0.269 | neutral | None | None | None | None | N |
| D/V | 0.1621 | likely_benign | 0.1759 | benign | 0.187 | Stabilizing | 0.521 | D | 0.313 | neutral | N | 0.48266114 | None | None | N |
| D/W | 0.8212 | likely_pathogenic | 0.8397 | pathogenic | -0.026 | Destabilizing | 0.996 | D | 0.421 | neutral | None | None | None | None | N |
| D/Y | 0.218 | likely_benign | 0.2306 | benign | 0.141 | Stabilizing | 0.979 | D | 0.33 | neutral | N | 0.467683984 | 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.