Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23234 | 69925;69926;69927 | chr2:178576544;178576543;178576542 | chr2:179441271;179441270;179441269 |
| N2AB | 21593 | 65002;65003;65004 | chr2:178576544;178576543;178576542 | chr2:179441271;179441270;179441269 |
| N2A | 20666 | 62221;62222;62223 | chr2:178576544;178576543;178576542 | chr2:179441271;179441270;179441269 |
| N2B | 14169 | 42730;42731;42732 | chr2:178576544;178576543;178576542 | chr2:179441271;179441270;179441269 |
| Novex-1 | 14294 | 43105;43106;43107 | chr2:178576544;178576543;178576542 | chr2:179441271;179441270;179441269 |
| Novex-2 | 14361 | 43306;43307;43308 | chr2:178576544;178576543;178576542 | chr2:179441271;179441270;179441269 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/K | None | None | 0.007 | N | 0.586 | 0.177 | 0.448696893172 | 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 |
| M/L | None | None | None | N | 0.179 | 0.158 | 0.37281450598 | gnomAD-4.0.0 | 1.59263E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85968E-06 | 0 | 0 |
| M/T | rs1002453249  |
None | None | N | 0.257 | 0.14 | 0.500805711387 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/T | rs1002453249 |
None | None | N | 0.257 | 0.14 | 0.500805711387 | gnomAD-4.0.0 | 4.05988E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.81985E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5878 | likely_pathogenic | 0.5833 | pathogenic | -1.899 | Destabilizing | None | N | 0.29 | neutral | None | None | None | None | N |
| M/C | 0.7067 | likely_pathogenic | 0.5932 | pathogenic | -2.533 | Highly Destabilizing | None | N | 0.373 | neutral | None | None | None | None | N |
| M/D | 0.9969 | likely_pathogenic | 0.9979 | pathogenic | -2.354 | Highly Destabilizing | 0.009 | N | 0.678 | prob.neutral | None | None | None | None | N |
| M/E | 0.9729 | likely_pathogenic | 0.9807 | pathogenic | -2.174 | Highly Destabilizing | 0.009 | N | 0.63 | neutral | None | None | None | None | N |
| M/F | 0.7634 | likely_pathogenic | 0.7633 | pathogenic | -0.626 | Destabilizing | 0.021 | N | 0.553 | neutral | None | None | None | None | N |
| M/G | 0.9295 | likely_pathogenic | 0.9367 | pathogenic | -2.281 | Highly Destabilizing | 0.002 | N | 0.597 | neutral | None | None | None | None | N |
| M/H | 0.9838 | likely_pathogenic | 0.9866 | pathogenic | -1.926 | Destabilizing | 0.314 | N | 0.658 | prob.neutral | None | None | None | None | N |
| M/I | 0.444 | ambiguous | 0.5543 | ambiguous | -0.825 | Destabilizing | None | N | 0.104 | neutral | N | 0.368000417 | None | None | N |
| M/K | 0.9308 | likely_pathogenic | 0.9495 | pathogenic | -1.358 | Destabilizing | 0.007 | N | 0.586 | neutral | N | 0.463102735 | None | None | N |
| M/L | 0.2554 | likely_benign | 0.2954 | benign | -0.825 | Destabilizing | None | N | 0.179 | neutral | N | 0.386063316 | None | None | N |
| M/N | 0.9591 | likely_pathogenic | 0.9699 | pathogenic | -1.676 | Destabilizing | 0.009 | N | 0.629 | neutral | None | None | None | None | N |
| M/P | 0.9127 | likely_pathogenic | 0.9102 | pathogenic | -1.165 | Destabilizing | 0.017 | N | 0.612 | neutral | None | None | None | None | N |
| M/Q | 0.8382 | likely_pathogenic | 0.8622 | pathogenic | -1.478 | Destabilizing | 0.041 | N | 0.56 | neutral | None | None | None | None | N |
| M/R | 0.9257 | likely_pathogenic | 0.9423 | pathogenic | -1.396 | Destabilizing | 0.007 | N | 0.631 | neutral | N | 0.474666523 | None | None | N |
| M/S | 0.8376 | likely_pathogenic | 0.8578 | pathogenic | -2.131 | Highly Destabilizing | None | N | 0.298 | neutral | None | None | None | None | N |
| M/T | 0.6135 | likely_pathogenic | 0.6543 | pathogenic | -1.843 | Destabilizing | None | N | 0.257 | neutral | N | 0.342141968 | None | None | N |
| M/V | 0.1778 | likely_benign | 0.2067 | benign | -1.165 | Destabilizing | None | N | 0.207 | neutral | N | 0.364325394 | None | None | N |
| M/W | 0.9863 | likely_pathogenic | 0.987 | pathogenic | -0.966 | Destabilizing | 0.314 | N | 0.575 | neutral | None | None | None | None | N |
| M/Y | 0.9797 | likely_pathogenic | 0.9812 | pathogenic | -0.867 | Destabilizing | 0.041 | N | 0.663 | 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.