Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21609 | 65050;65051;65052 | chr2:178584816;178584815;178584814 | chr2:179449543;179449542;179449541 |
| N2AB | 19968 | 60127;60128;60129 | chr2:178584816;178584815;178584814 | chr2:179449543;179449542;179449541 |
| N2A | 19041 | 57346;57347;57348 | chr2:178584816;178584815;178584814 | chr2:179449543;179449542;179449541 |
| N2B | 12544 | 37855;37856;37857 | chr2:178584816;178584815;178584814 | chr2:179449543;179449542;179449541 |
| Novex-1 | 12669 | 38230;38231;38232 | chr2:178584816;178584815;178584814 | chr2:179449543;179449542;179449541 |
| Novex-2 | 12736 | 38431;38432;38433 | chr2:178584816;178584815;178584814 | chr2:179449543;179449542;179449541 |
| 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/A | None | None | 0.91 | N | 0.416 | 0.158 | 0.26169431596 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| T/M | rs765913263  |
0.126 | 1.0 | N | 0.663 | 0.409 | 0.667756737924 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | N | None | 1.241E-04 | 0 | None | 0 | 5.14E-05 | None | 0 | None | 0 | 7.84E-06 | 0 |
| T/M | rs765913263 |
0.126 | 1.0 | N | 0.663 | 0.409 | 0.667756737924 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/M | rs765913263 |
0.126 | 1.0 | N | 0.663 | 0.409 | 0.667756737924 | gnomAD-4.0.0 | 1.23974E-05 | None | None | None | None | N | None | 8.01625E-05 | 0 | None | 0 | 2.23115E-05 | None | 0 | 0 | 1.01735E-05 | 0 | 1.60169E-05 |
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 | 0.0939 | likely_benign | 0.0962 | benign | -0.498 | Destabilizing | 0.91 | D | 0.416 | neutral | N | 0.51419049 | None | None | N |
| T/C | 0.4057 | ambiguous | 0.3959 | ambiguous | -0.38 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | N |
| T/D | 0.662 | likely_pathogenic | 0.6938 | pathogenic | -0.093 | Destabilizing | 0.996 | D | 0.579 | neutral | None | None | None | None | N |
| T/E | 0.4695 | ambiguous | 0.5187 | ambiguous | -0.13 | Destabilizing | 0.996 | D | 0.579 | neutral | None | None | None | None | N |
| T/F | 0.3844 | ambiguous | 0.3913 | ambiguous | -0.682 | Destabilizing | 0.991 | D | 0.709 | prob.delet. | None | None | None | None | N |
| T/G | 0.366 | ambiguous | 0.3816 | ambiguous | -0.71 | Destabilizing | 0.996 | D | 0.565 | neutral | None | None | None | None | N |
| T/H | 0.4147 | ambiguous | 0.4343 | ambiguous | -0.989 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | N |
| T/I | 0.1513 | likely_benign | 0.1593 | benign | -0.043 | Destabilizing | 0.503 | D | 0.293 | neutral | None | None | None | None | N |
| T/K | 0.3574 | ambiguous | 0.4324 | ambiguous | -0.685 | Destabilizing | 0.998 | D | 0.58 | neutral | N | 0.496412806 | None | None | N |
| T/L | 0.091 | likely_benign | 0.0921 | benign | -0.043 | Destabilizing | 0.942 | D | 0.46 | neutral | None | None | None | None | N |
| T/M | 0.08 | likely_benign | 0.0808 | benign | 0.115 | Stabilizing | 1.0 | D | 0.663 | neutral | N | 0.519001664 | None | None | N |
| T/N | 0.1823 | likely_benign | 0.185 | benign | -0.513 | Destabilizing | 0.999 | D | 0.561 | neutral | None | None | None | None | N |
| T/P | 0.0964 | likely_benign | 0.0953 | benign | -0.163 | Destabilizing | 0.071 | N | 0.311 | neutral | N | 0.477269684 | None | None | N |
| T/Q | 0.3024 | likely_benign | 0.3362 | benign | -0.702 | Destabilizing | 0.999 | D | 0.659 | neutral | None | None | None | None | N |
| T/R | 0.3316 | likely_benign | 0.399 | ambiguous | -0.398 | Destabilizing | 0.999 | D | 0.66 | neutral | N | 0.513843773 | None | None | N |
| T/S | 0.1667 | likely_benign | 0.1653 | benign | -0.734 | Destabilizing | 0.98 | D | 0.435 | neutral | N | 0.512611622 | None | None | N |
| T/V | 0.1153 | likely_benign | 0.1202 | benign | -0.163 | Destabilizing | 0.942 | D | 0.416 | neutral | None | None | None | None | N |
| T/W | 0.741 | likely_pathogenic | 0.7462 | pathogenic | -0.662 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| T/Y | 0.4225 | ambiguous | 0.4283 | ambiguous | -0.424 | Destabilizing | 0.999 | D | 0.705 | prob.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.