Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15158 | 45697;45698;45699 | chr2:178621246;178621245;178621244 | chr2:179485973;179485972;179485971 |
| N2AB | 13517 | 40774;40775;40776 | chr2:178621246;178621245;178621244 | chr2:179485973;179485972;179485971 |
| N2A | 12590 | 37993;37994;37995 | chr2:178621246;178621245;178621244 | chr2:179485973;179485972;179485971 |
| N2B | 6093 | 18502;18503;18504 | chr2:178621246;178621245;178621244 | chr2:179485973;179485972;179485971 |
| Novex-1 | 6218 | 18877;18878;18879 | chr2:178621246;178621245;178621244 | chr2:179485973;179485972;179485971 |
| Novex-2 | 6285 | 19078;19079;19080 | chr2:178621246;178621245;178621244 | chr2:179485973;179485972;179485971 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs371879778  |
-0.07 | None | N | 0.19 | 0.117 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 1.24244E-04 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/I | rs371879778 |
-0.07 | None | N | 0.19 | 0.117 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 7.25E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.42E-05 | 0 | 0 |
| T/I | rs371879778 |
-0.07 | None | N | 0.19 | 0.117 | None | gnomAD-4.0.0 | 1.24058E-05 | None | None | None | None | N | None | 5.34817E-05 | 3.34627E-05 | None | 0 | 0 | None | 0 | 0 | 1.01772E-05 | 2.19698E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0832 | likely_benign | 0.09 | benign | -0.443 | Destabilizing | 0.019 | N | 0.182 | neutral | N | 0.439474788 | None | None | N |
| T/C | 0.4628 | ambiguous | 0.3848 | ambiguous | -0.321 | Destabilizing | 0.859 | D | 0.362 | neutral | None | None | None | None | N |
| T/D | 0.3019 | likely_benign | 0.3004 | benign | 0.202 | Stabilizing | 0.055 | N | 0.346 | neutral | None | None | None | None | N |
| T/E | 0.2041 | likely_benign | 0.2019 | benign | 0.153 | Stabilizing | 0.002 | N | 0.159 | neutral | None | None | None | None | N |
| T/F | 0.1952 | likely_benign | 0.189 | benign | -0.685 | Destabilizing | 0.497 | N | 0.469 | neutral | None | None | None | None | N |
| T/G | 0.3046 | likely_benign | 0.2948 | benign | -0.633 | Destabilizing | 0.104 | N | 0.343 | neutral | None | None | None | None | N |
| T/H | 0.2414 | likely_benign | 0.2337 | benign | -0.872 | Destabilizing | 0.667 | D | 0.412 | neutral | None | None | None | None | N |
| T/I | 0.0756 | likely_benign | 0.0751 | benign | -0.051 | Destabilizing | None | N | 0.19 | neutral | N | 0.423391183 | None | None | N |
| T/K | 0.1835 | likely_benign | 0.1633 | benign | -0.505 | Destabilizing | None | N | 0.181 | neutral | N | 0.429483707 | None | None | N |
| T/L | 0.0752 | likely_benign | 0.0752 | benign | -0.051 | Destabilizing | 0.009 | N | 0.266 | neutral | None | None | None | None | N |
| T/M | 0.069 | likely_benign | 0.0737 | benign | 0.061 | Stabilizing | 0.497 | N | 0.377 | neutral | None | None | None | None | N |
| T/N | 0.0927 | likely_benign | 0.1031 | benign | -0.274 | Destabilizing | 0.22 | N | 0.221 | neutral | None | None | None | None | N |
| T/P | 0.0895 | likely_benign | 0.0958 | benign | -0.151 | Destabilizing | None | N | 0.184 | neutral | N | 0.370947404 | None | None | N |
| T/Q | 0.1768 | likely_benign | 0.176 | benign | -0.477 | Destabilizing | 0.124 | N | 0.364 | neutral | None | None | None | None | N |
| T/R | 0.1821 | likely_benign | 0.1684 | benign | -0.231 | Destabilizing | 0.096 | N | 0.381 | neutral | N | 0.463912919 | None | None | N |
| T/S | 0.1192 | likely_benign | 0.1279 | benign | -0.541 | Destabilizing | 0.042 | N | 0.205 | neutral | N | 0.470410249 | None | None | N |
| T/V | 0.0852 | likely_benign | 0.0857 | benign | -0.151 | Destabilizing | None | N | 0.113 | neutral | None | None | None | None | N |
| T/W | 0.5838 | likely_pathogenic | 0.5427 | ambiguous | -0.655 | Destabilizing | 0.958 | D | 0.41 | neutral | None | None | None | None | N |
| T/Y | 0.2594 | likely_benign | 0.239 | benign | -0.407 | Destabilizing | 0.667 | D | 0.461 | 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.