Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35139 | 105640;105641;105642 | chr2:178531200;178531199;178531198 | chr2:179395927;179395926;179395925 |
| N2AB | 33498 | 100717;100718;100719 | chr2:178531200;178531199;178531198 | chr2:179395927;179395926;179395925 |
| N2A | 32571 | 97936;97937;97938 | chr2:178531200;178531199;178531198 | chr2:179395927;179395926;179395925 |
| N2B | 26074 | 78445;78446;78447 | chr2:178531200;178531199;178531198 | chr2:179395927;179395926;179395925 |
| Novex-1 | 26199 | 78820;78821;78822 | chr2:178531200;178531199;178531198 | chr2:179395927;179395926;179395925 |
| Novex-2 | 26266 | 79021;79022;79023 | chr2:178531200;178531199;178531198 | chr2:179395927;179395926;179395925 |
| 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 | rs200782068  |
0.061 | 1.0 | N | 0.694 | 0.403 | None | gnomAD-2.1.1 | 4.28E-05 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 0 | None | 3.27E-05 | None | 4E-05 | 6.24E-05 | 1.40174E-04 |
| T/I | rs200782068 |
0.061 | 1.0 | N | 0.694 | 0.403 | None | gnomAD-3.1.2 | 7.89E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47003E-04 | 0 | 0 |
| T/I | rs200782068 |
0.061 | 1.0 | N | 0.694 | 0.403 | None | gnomAD-4.0.0 | 4.58525E-05 | None | None | None | None | N | None | 2.66987E-05 | 1.6665E-05 | None | 0 | 0 | None | 1.56206E-05 | 1.15056E-03 | 4.15294E-05 | 1.31744E-04 | 3.20174E-05 |
| T/N | None | None | 1.0 | N | 0.685 | 0.317 | 0.503683571763 | gnomAD-4.0.0 | 6.84135E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99392E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0984 | likely_benign | 0.0986 | benign | -0.713 | Destabilizing | 0.999 | D | 0.505 | neutral | N | 0.503928716 | None | None | N |
| T/C | 0.6858 | likely_pathogenic | 0.635 | pathogenic | -0.436 | Destabilizing | 1.0 | D | 0.596 | neutral | None | None | None | None | N |
| T/D | 0.4874 | ambiguous | 0.4862 | ambiguous | 0.15 | Stabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| T/E | 0.3363 | likely_benign | 0.3491 | ambiguous | 0.142 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| T/F | 0.3138 | likely_benign | 0.3105 | benign | -0.86 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| T/G | 0.4167 | ambiguous | 0.4189 | ambiguous | -0.949 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| T/H | 0.3401 | ambiguous | 0.3298 | benign | -1.163 | Destabilizing | 1.0 | D | 0.632 | neutral | None | None | None | None | N |
| T/I | 0.1771 | likely_benign | 0.1807 | benign | -0.185 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | N | 0.494541228 | None | None | N |
| T/K | 0.2411 | likely_benign | 0.2379 | benign | -0.593 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| T/L | 0.1268 | likely_benign | 0.126 | benign | -0.185 | Destabilizing | 0.999 | D | 0.668 | neutral | None | None | None | None | N |
| T/M | 0.0925 | likely_benign | 0.0941 | benign | -0.058 | Destabilizing | 1.0 | D | 0.609 | neutral | None | None | None | None | N |
| T/N | 0.164 | likely_benign | 0.1618 | benign | -0.506 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | N | 0.492569318 | None | None | N |
| T/P | 0.2525 | likely_benign | 0.2598 | benign | -0.329 | Destabilizing | 1.0 | D | 0.674 | neutral | N | 0.502799988 | None | None | N |
| T/Q | 0.2639 | likely_benign | 0.2721 | benign | -0.622 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | N |
| T/R | 0.1893 | likely_benign | 0.1868 | benign | -0.381 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| T/S | 0.1544 | likely_benign | 0.1574 | benign | -0.797 | Destabilizing | 0.999 | D | 0.543 | neutral | N | 0.509931968 | None | None | N |
| T/V | 0.153 | likely_benign | 0.1498 | benign | -0.329 | Destabilizing | 0.999 | D | 0.6 | neutral | None | None | None | None | N |
| T/W | 0.6704 | likely_pathogenic | 0.663 | pathogenic | -0.821 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| T/Y | 0.4153 | ambiguous | 0.3901 | ambiguous | -0.578 | Destabilizing | 1.0 | D | 0.682 | 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.