Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29270 | 88033;88034;88035 | chr2:178557454;178557453;178557452 | chr2:179422181;179422180;179422179 |
| N2AB | 27629 | 83110;83111;83112 | chr2:178557454;178557453;178557452 | chr2:179422181;179422180;179422179 |
| N2A | 26702 | 80329;80330;80331 | chr2:178557454;178557453;178557452 | chr2:179422181;179422180;179422179 |
| N2B | 20205 | 60838;60839;60840 | chr2:178557454;178557453;178557452 | chr2:179422181;179422180;179422179 |
| Novex-1 | 20330 | 61213;61214;61215 | chr2:178557454;178557453;178557452 | chr2:179422181;179422180;179422179 |
| Novex-2 | 20397 | 61414;61415;61416 | chr2:178557454;178557453;178557452 | chr2:179422181;179422180;179422179 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs141624266  |
-0.305 | None | N | 0.067 | 0.056 | None | gnomAD-2.1.1 | 4.02322E-03 | None | None | None | None | I | None | 3.71962E-04 | 2.82773E-04 | None | 0 | 5.13E-05 | None | 4.77093E-03 | None | 2.63768E-02 | 2.15659E-03 | 3.50828E-03 |
| V/I | rs141624266 |
-0.305 | None | N | 0.067 | 0.056 | None | gnomAD-3.1.2 | 3.13473E-03 | None | None | None | None | I | None | 2.17161E-04 | 5.23629E-04 | 0 | 0 | 0 | None | 2.72333E-02 | 0 | 2.13141E-03 | 4.96689E-03 | 9.57854E-04 |
| V/I | rs141624266 |
-0.305 | None | N | 0.067 | 0.056 | None | 1000 genomes | 2.59585E-03 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 6E-03 | None | None | None | 7.2E-03 | None |
| V/I | rs141624266 |
-0.305 | None | N | 0.067 | 0.056 | None | gnomAD-4.0.0 | 2.95804E-03 | None | None | None | None | I | None | 3.99755E-04 | 3.16551E-04 | None | 3.04013E-04 | 4.45971E-05 | None | 2.69645E-02 | 1.48515E-03 | 2.01976E-03 | 5.08322E-03 | 2.12868E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0846 | likely_benign | 0.1027 | benign | -0.797 | Destabilizing | 0.012 | N | 0.216 | neutral | N | 0.482694147 | None | None | I |
| V/C | 0.4191 | ambiguous | 0.5051 | ambiguous | -0.696 | Destabilizing | 0.356 | N | 0.291 | neutral | None | None | None | None | I |
| V/D | 0.2988 | likely_benign | 0.4027 | ambiguous | -0.588 | Destabilizing | 0.214 | N | 0.397 | neutral | None | None | None | None | I |
| V/E | 0.2444 | likely_benign | 0.322 | benign | -0.687 | Destabilizing | 0.055 | N | 0.348 | neutral | N | 0.452717957 | None | None | I |
| V/F | 0.0809 | likely_benign | 0.0903 | benign | -0.85 | Destabilizing | None | N | 0.187 | neutral | None | None | None | None | I |
| V/G | 0.1515 | likely_benign | 0.2183 | benign | -0.978 | Destabilizing | 0.055 | N | 0.347 | neutral | N | 0.465321894 | None | None | I |
| V/H | 0.2947 | likely_benign | 0.3644 | ambiguous | -0.479 | Destabilizing | 0.628 | D | 0.277 | neutral | None | None | None | None | I |
| V/I | 0.053 | likely_benign | 0.0523 | benign | -0.458 | Destabilizing | None | N | 0.067 | neutral | N | 0.354191332 | None | None | I |
| V/K | 0.2486 | likely_benign | 0.3152 | benign | -0.719 | Destabilizing | 0.072 | N | 0.359 | neutral | None | None | None | None | I |
| V/L | 0.0753 | likely_benign | 0.0876 | benign | -0.458 | Destabilizing | None | N | 0.088 | neutral | N | 0.361423949 | None | None | I |
| V/M | 0.0721 | likely_benign | 0.0817 | benign | -0.388 | Destabilizing | 0.002 | N | 0.157 | neutral | None | None | None | None | I |
| V/N | 0.1425 | likely_benign | 0.19 | benign | -0.415 | Destabilizing | 0.214 | N | 0.377 | neutral | None | None | None | None | I |
| V/P | 0.6 | likely_pathogenic | 0.6673 | pathogenic | -0.535 | Destabilizing | 0.356 | N | 0.364 | neutral | None | None | None | None | I |
| V/Q | 0.2076 | likely_benign | 0.2656 | benign | -0.688 | Destabilizing | 0.356 | N | 0.305 | neutral | None | None | None | None | I |
| V/R | 0.1855 | likely_benign | 0.2277 | benign | -0.124 | Destabilizing | 0.214 | N | 0.379 | neutral | None | None | None | None | I |
| V/S | 0.0945 | likely_benign | 0.1234 | benign | -0.817 | Destabilizing | 0.038 | N | 0.285 | neutral | None | None | None | None | I |
| V/T | 0.0604 | likely_benign | 0.07 | benign | -0.818 | Destabilizing | None | N | 0.131 | neutral | None | None | None | None | I |
| V/W | 0.4784 | ambiguous | 0.5628 | ambiguous | -0.915 | Destabilizing | 0.864 | D | 0.283 | neutral | None | None | None | None | I |
| V/Y | 0.3002 | likely_benign | 0.377 | ambiguous | -0.643 | Destabilizing | 0.038 | N | 0.348 | neutral | None | None | None | None | I |
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.