Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3280 | 10063;10064;10065 | chr2:178764677;178764676;178764675 | chr2:179629404;179629403;179629402 |
| N2AB | 3280 | 10063;10064;10065 | chr2:178764677;178764676;178764675 | chr2:179629404;179629403;179629402 |
| N2A | 3280 | 10063;10064;10065 | chr2:178764677;178764676;178764675 | chr2:179629404;179629403;179629402 |
| N2B | 3234 | 9925;9926;9927 | chr2:178764677;178764676;178764675 | chr2:179629404;179629403;179629402 |
| Novex-1 | 3234 | 9925;9926;9927 | chr2:178764677;178764676;178764675 | chr2:179629404;179629403;179629402 |
| Novex-2 | 3234 | 9925;9926;9927 | chr2:178764677;178764676;178764675 | chr2:179629404;179629403;179629402 |
| Novex-3 | 3280 | 10063;10064;10065 | chr2:178764677;178764676;178764675 | chr2:179629404;179629403;179629402 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | None | None | 1.0 | D | 0.492 | 0.497 | 0.498387242485 | gnomAD-4.0.0 | 6.84067E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99294E-07 | 0 | 0 |
| S/F | rs747768723  |
-0.863 | 0.999 | D | 0.569 | 0.545 | 0.659558603232 | gnomAD-2.1.1 | 7.08E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.77E-06 | 1.38658E-04 |
| S/F | rs747768723 |
-0.863 | 0.999 | D | 0.569 | 0.545 | 0.659558603232 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 0 | 0 | 0 |
| S/F | rs747768723 |
-0.863 | 0.999 | D | 0.569 | 0.545 | 0.659558603232 | gnomAD-4.0.0 | 1.85869E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.6442E-04 | 1.69489E-06 | 0 | 0 |
| S/P | None | None | 0.999 | N | 0.43 | 0.514 | 0.377976839388 | gnomAD-4.0.0 | 1.59049E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77331E-05 | None | 0 | 0 | 0 | 0 | 0 |
| S/Y | rs747768723 |
-0.595 | 0.999 | D | 0.569 | 0.558 | 0.679525051678 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.82E-06 | 0 |
| S/Y | rs747768723 |
-0.595 | 0.999 | D | 0.569 | 0.558 | 0.679525051678 | gnomAD-4.0.0 | 4.1044E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39576E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1274 | likely_benign | 0.1583 | benign | -0.236 | Destabilizing | 0.953 | D | 0.374 | neutral | N | 0.506196247 | None | None | I |
| S/C | 0.3035 | likely_benign | 0.4175 | ambiguous | -0.453 | Destabilizing | 1.0 | D | 0.492 | neutral | D | 0.630839908 | None | None | I |
| S/D | 0.7429 | likely_pathogenic | 0.8087 | pathogenic | 0.425 | Stabilizing | 0.985 | D | 0.353 | neutral | None | None | None | None | I |
| S/E | 0.7999 | likely_pathogenic | 0.8434 | pathogenic | 0.35 | Stabilizing | 0.971 | D | 0.367 | neutral | None | None | None | None | I |
| S/F | 0.4917 | ambiguous | 0.6284 | pathogenic | -0.969 | Destabilizing | 0.999 | D | 0.569 | neutral | D | 0.578408057 | None | None | I |
| S/G | 0.1783 | likely_benign | 0.2487 | benign | -0.306 | Destabilizing | 0.993 | D | 0.367 | neutral | None | None | None | None | I |
| S/H | 0.587 | likely_pathogenic | 0.6806 | pathogenic | -0.541 | Destabilizing | 0.999 | D | 0.452 | neutral | None | None | None | None | I |
| S/I | 0.51 | ambiguous | 0.6269 | pathogenic | -0.18 | Destabilizing | 0.996 | D | 0.549 | neutral | None | None | None | None | I |
| S/K | 0.8972 | likely_pathogenic | 0.9335 | pathogenic | -0.191 | Destabilizing | 0.971 | D | 0.347 | neutral | None | None | None | None | I |
| S/L | 0.2227 | likely_benign | 0.3117 | benign | -0.18 | Destabilizing | 0.985 | D | 0.466 | neutral | None | None | None | None | I |
| S/M | 0.4304 | ambiguous | 0.5097 | ambiguous | -0.341 | Destabilizing | 1.0 | D | 0.451 | neutral | None | None | None | None | I |
| S/N | 0.2827 | likely_benign | 0.3917 | ambiguous | -0.112 | Destabilizing | 0.993 | D | 0.39 | neutral | None | None | None | None | I |
| S/P | 0.349 | ambiguous | 0.4992 | ambiguous | -0.174 | Destabilizing | 0.999 | D | 0.43 | neutral | N | 0.515418015 | None | None | I |
| S/Q | 0.709 | likely_pathogenic | 0.7683 | pathogenic | -0.227 | Destabilizing | 0.856 | D | 0.214 | neutral | None | None | None | None | I |
| S/R | 0.8402 | likely_pathogenic | 0.9025 | pathogenic | -0.009 | Destabilizing | 0.996 | D | 0.384 | neutral | None | None | None | None | I |
| S/T | 0.1253 | likely_benign | 0.1459 | benign | -0.202 | Destabilizing | 0.4 | N | 0.226 | neutral | N | 0.510709663 | None | None | I |
| S/V | 0.4316 | ambiguous | 0.5357 | ambiguous | -0.174 | Destabilizing | 0.985 | D | 0.446 | neutral | None | None | None | None | I |
| S/W | 0.7031 | likely_pathogenic | 0.7739 | pathogenic | -1.067 | Destabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | I |
| S/Y | 0.4639 | ambiguous | 0.5602 | ambiguous | -0.718 | Destabilizing | 0.999 | D | 0.569 | neutral | D | 0.659272737 | 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.