Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19873 | 59842;59843;59844 | chr2:178592388;178592387;178592386 | chr2:179457115;179457114;179457113 |
| N2AB | 18232 | 54919;54920;54921 | chr2:178592388;178592387;178592386 | chr2:179457115;179457114;179457113 |
| N2A | 17305 | 52138;52139;52140 | chr2:178592388;178592387;178592386 | chr2:179457115;179457114;179457113 |
| N2B | 10808 | 32647;32648;32649 | chr2:178592388;178592387;178592386 | chr2:179457115;179457114;179457113 |
| Novex-1 | 10933 | 33022;33023;33024 | chr2:178592388;178592387;178592386 | chr2:179457115;179457114;179457113 |
| Novex-2 | 11000 | 33223;33224;33225 | chr2:178592388;178592387;178592386 | chr2:179457115;179457114;179457113 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | None | None | 0.003 | N | 0.275 | 0.177 | 0.62963637804 | gnomAD-4.0.0 | 6.84901E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99784E-07 | 0 | 0 |
| L/P | rs727503589  |
-0.439 | 0.912 | N | 0.588 | 0.48 | 0.86720306763 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.68E-05 | 0 |
| L/P | rs727503589 |
-0.439 | 0.912 | N | 0.588 | 0.48 | 0.86720306763 | gnomAD-4.0.0 | 8.21947E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.07973E-05 | 0 | 0 |
| L/V | rs1185370817 |
-0.299 | 0.001 | N | 0.127 | 0.057 | 0.50343701615 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.31E-05 | None | 0 | 0 | 0 |
| L/V | rs1185370817 |
-0.299 | 0.001 | N | 0.127 | 0.057 | 0.50343701615 | gnomAD-4.0.0 | 6.84901E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65832E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.1928 | likely_benign | 0.219 | benign | -2.039 | Highly Destabilizing | 0.241 | N | 0.379 | neutral | None | None | None | None | N |
| L/C | 0.4858 | ambiguous | 0.5144 | ambiguous | -1.038 | Destabilizing | 0.944 | D | 0.483 | neutral | None | None | None | None | N |
| L/D | 0.653 | likely_pathogenic | 0.7373 | pathogenic | -1.712 | Destabilizing | 0.527 | D | 0.566 | neutral | None | None | None | None | N |
| L/E | 0.3615 | ambiguous | 0.4253 | ambiguous | -1.683 | Destabilizing | 0.69 | D | 0.558 | neutral | None | None | None | None | N |
| L/F | 0.146 | likely_benign | 0.1577 | benign | -1.407 | Destabilizing | 0.003 | N | 0.275 | neutral | N | 0.50002483 | None | None | N |
| L/G | 0.556 | ambiguous | 0.6186 | pathogenic | -2.4 | Highly Destabilizing | 0.69 | D | 0.495 | neutral | None | None | None | None | N |
| L/H | 0.2028 | likely_benign | 0.2373 | benign | -1.618 | Destabilizing | 0.928 | D | 0.583 | neutral | N | 0.498002821 | None | None | N |
| L/I | 0.0639 | likely_benign | 0.0625 | benign | -1.089 | Destabilizing | 0.001 | N | 0.278 | neutral | N | 0.490114057 | None | None | N |
| L/K | 0.2309 | likely_benign | 0.2754 | benign | -1.504 | Destabilizing | 0.69 | D | 0.497 | neutral | None | None | None | None | N |
| L/M | 0.0929 | likely_benign | 0.0886 | benign | -0.713 | Destabilizing | 0.69 | D | 0.461 | neutral | None | None | None | None | N |
| L/N | 0.2856 | likely_benign | 0.3288 | benign | -1.297 | Destabilizing | 0.019 | N | 0.459 | neutral | None | None | None | None | N |
| L/P | 0.9344 | likely_pathogenic | 0.9467 | pathogenic | -1.378 | Destabilizing | 0.912 | D | 0.588 | neutral | N | 0.511634625 | None | None | N |
| L/Q | 0.137 | likely_benign | 0.1547 | benign | -1.468 | Destabilizing | 0.818 | D | 0.563 | neutral | None | None | None | None | N |
| L/R | 0.1695 | likely_benign | 0.2142 | benign | -0.845 | Destabilizing | 0.773 | D | 0.549 | neutral | N | 0.486708392 | None | None | N |
| L/S | 0.2471 | likely_benign | 0.2895 | benign | -1.893 | Destabilizing | 0.69 | D | 0.461 | neutral | None | None | None | None | N |
| L/T | 0.1389 | likely_benign | 0.1548 | benign | -1.755 | Destabilizing | 0.388 | N | 0.415 | neutral | None | None | None | None | N |
| L/V | 0.0602 | likely_benign | 0.0611 | benign | -1.378 | Destabilizing | 0.001 | N | 0.127 | neutral | N | 0.471797655 | None | None | N |
| L/W | 0.309 | likely_benign | 0.347 | ambiguous | -1.54 | Destabilizing | 0.944 | D | 0.622 | neutral | None | None | None | None | N |
| L/Y | 0.3479 | ambiguous | 0.3822 | ambiguous | -1.348 | Destabilizing | 0.527 | 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.