Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22712 | 68359;68360;68361 | chr2:178578896;178578895;178578894 | chr2:179443623;179443622;179443621 |
| N2AB | 21071 | 63436;63437;63438 | chr2:178578896;178578895;178578894 | chr2:179443623;179443622;179443621 |
| N2A | 20144 | 60655;60656;60657 | chr2:178578896;178578895;178578894 | chr2:179443623;179443622;179443621 |
| N2B | 13647 | 41164;41165;41166 | chr2:178578896;178578895;178578894 | chr2:179443623;179443622;179443621 |
| Novex-1 | 13772 | 41539;41540;41541 | chr2:178578896;178578895;178578894 | chr2:179443623;179443622;179443621 |
| Novex-2 | 13839 | 41740;41741;41742 | chr2:178578896;178578895;178578894 | chr2:179443623;179443622;179443621 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs777200566  |
-0.936 | None | N | 0.076 | 0.099 | 0.448696893172 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 1.29249E-04 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| M/I | rs777200566 |
-0.936 | None | N | 0.076 | 0.099 | 0.448696893172 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/I | rs777200566 |
-0.936 | None | N | 0.076 | 0.099 | 0.448696893172 | gnomAD-4.0.0 | 4.33923E-06 | None | None | None | None | N | None | 8.01325E-05 | 0 | None | 0 | 2.23234E-05 | None | 0 | 0 | 0 | 0 | 0 |
| M/V | rs1223811231 |
None | None | N | 0.071 | 0.064 | 0.167679373172 | 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 |
| M/V | rs1223811231 |
None | None | N | 0.071 | 0.064 | 0.167679373172 | gnomAD-4.0.0 | 4.06011E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.81999E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.2202 | likely_benign | 0.1351 | benign | -2.617 | Highly Destabilizing | None | N | 0.28 | neutral | None | None | None | None | N |
| M/C | 0.4363 | ambiguous | 0.3812 | ambiguous | -1.344 | Destabilizing | 0.132 | N | 0.311 | neutral | None | None | None | None | N |
| M/D | 0.6395 | likely_pathogenic | 0.4966 | ambiguous | -1.287 | Destabilizing | 0.002 | N | 0.289 | neutral | None | None | None | None | N |
| M/E | 0.3529 | ambiguous | 0.2689 | benign | -1.219 | Destabilizing | 0.002 | N | 0.255 | neutral | None | None | None | None | N |
| M/F | 0.2757 | likely_benign | 0.2101 | benign | -1.393 | Destabilizing | 0.004 | N | 0.199 | neutral | None | None | None | None | N |
| M/G | 0.4567 | ambiguous | 0.2984 | benign | -2.968 | Highly Destabilizing | 0.002 | N | 0.251 | neutral | None | None | None | None | N |
| M/H | 0.3484 | ambiguous | 0.259 | benign | -2.035 | Highly Destabilizing | 0.132 | N | 0.379 | neutral | None | None | None | None | N |
| M/I | 0.174 | likely_benign | 0.1243 | benign | -1.654 | Destabilizing | None | N | 0.076 | neutral | N | 0.447312137 | None | None | N |
| M/K | 0.1563 | likely_benign | 0.1177 | benign | -1.241 | Destabilizing | None | N | 0.164 | neutral | N | 0.381279146 | None | None | N |
| M/L | 0.1165 | likely_benign | 0.0889 | benign | -1.654 | Destabilizing | None | N | 0.069 | neutral | N | 0.456835697 | None | None | N |
| M/N | 0.2171 | likely_benign | 0.1511 | benign | -1.073 | Destabilizing | None | N | 0.175 | neutral | None | None | None | None | N |
| M/P | 0.9306 | likely_pathogenic | 0.8236 | pathogenic | -1.954 | Destabilizing | 0.018 | N | 0.291 | neutral | None | None | None | None | N |
| M/Q | 0.1761 | likely_benign | 0.1454 | benign | -1.111 | Destabilizing | 0.009 | N | 0.221 | neutral | None | None | None | None | N |
| M/R | 0.1749 | likely_benign | 0.1192 | benign | -0.76 | Destabilizing | 0.003 | N | 0.294 | neutral | N | 0.38606889 | None | None | N |
| M/S | 0.2109 | likely_benign | 0.1382 | benign | -1.712 | Destabilizing | None | N | 0.157 | neutral | None | None | None | None | N |
| M/T | 0.1082 | likely_benign | 0.0709 | benign | -1.54 | Destabilizing | None | N | 0.154 | neutral | N | 0.341195031 | None | None | N |
| M/V | 0.0761 | likely_benign | 0.0604 | benign | -1.954 | Destabilizing | None | N | 0.071 | neutral | N | 0.398056752 | None | None | N |
| M/W | 0.5518 | ambiguous | 0.4424 | ambiguous | -1.331 | Destabilizing | 0.316 | N | 0.332 | neutral | None | None | None | None | N |
| M/Y | 0.4266 | ambiguous | 0.3505 | ambiguous | -1.478 | Destabilizing | 0.041 | N | 0.333 | neutral | None | None | 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.