Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27031 | 81316;81317;81318 | chr2:178565041;178565040;178565039 | chr2:179429768;179429767;179429766 |
| N2AB | 25390 | 76393;76394;76395 | chr2:178565041;178565040;178565039 | chr2:179429768;179429767;179429766 |
| N2A | 24463 | 73612;73613;73614 | chr2:178565041;178565040;178565039 | chr2:179429768;179429767;179429766 |
| N2B | 17966 | 54121;54122;54123 | chr2:178565041;178565040;178565039 | chr2:179429768;179429767;179429766 |
| Novex-1 | 18091 | 54496;54497;54498 | chr2:178565041;178565040;178565039 | chr2:179429768;179429767;179429766 |
| Novex-2 | 18158 | 54697;54698;54699 | chr2:178565041;178565040;178565039 | chr2:179429768;179429767;179429766 |
| 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 | 0.63 | N | 0.448 | 0.237 | 0.24896430686 | gnomAD-4.0.0 | 1.36854E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87287E-05 | 0 | 8.99536E-07 | 0 | 0 |
| T/I | rs777849777  |
0.398 | 0.983 | N | 0.641 | 0.437 | 0.513394077459 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| T/I | rs777849777 |
0.398 | 0.983 | N | 0.641 | 0.437 | 0.513394077459 | gnomAD-4.0.0 | 5.47434E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.19635E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0918 | likely_benign | 0.0862 | benign | -0.888 | Destabilizing | 0.63 | D | 0.448 | neutral | N | 0.472155706 | None | None | N |
| T/C | 0.4656 | ambiguous | 0.4532 | ambiguous | -0.497 | Destabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | N |
| T/D | 0.6795 | likely_pathogenic | 0.6644 | pathogenic | -0.457 | Destabilizing | 0.975 | D | 0.622 | neutral | None | None | None | None | N |
| T/E | 0.5685 | likely_pathogenic | 0.5492 | ambiguous | -0.33 | Destabilizing | 0.845 | D | 0.56 | neutral | None | None | None | None | N |
| T/F | 0.4104 | ambiguous | 0.3695 | ambiguous | -0.678 | Destabilizing | 0.996 | D | 0.727 | prob.delet. | None | None | None | None | N |
| T/G | 0.3101 | likely_benign | 0.2738 | benign | -1.258 | Destabilizing | 0.845 | D | 0.569 | neutral | None | None | None | None | N |
| T/H | 0.3858 | ambiguous | 0.3606 | ambiguous | -1.418 | Destabilizing | 0.997 | D | 0.713 | prob.delet. | None | None | None | None | N |
| T/I | 0.3108 | likely_benign | 0.3028 | benign | 0.051 | Stabilizing | 0.983 | D | 0.641 | neutral | N | 0.483222524 | None | None | N |
| T/K | 0.3836 | ambiguous | 0.3715 | ambiguous | -0.443 | Destabilizing | 0.056 | N | 0.427 | neutral | N | 0.516846793 | None | None | N |
| T/L | 0.1645 | likely_benign | 0.1526 | benign | 0.051 | Stabilizing | 0.916 | D | 0.539 | neutral | None | None | None | None | N |
| T/M | 0.1051 | likely_benign | 0.0975 | benign | 0.047 | Stabilizing | 0.999 | D | 0.669 | neutral | None | None | None | None | N |
| T/N | 0.1686 | likely_benign | 0.1602 | benign | -0.802 | Destabilizing | 0.975 | D | 0.562 | neutral | None | None | None | None | N |
| T/P | 0.8181 | likely_pathogenic | 0.8221 | pathogenic | -0.229 | Destabilizing | 0.983 | D | 0.639 | neutral | N | 0.494489923 | None | None | N |
| T/Q | 0.3112 | likely_benign | 0.2902 | benign | -0.692 | Destabilizing | 0.975 | D | 0.641 | neutral | None | None | None | None | N |
| T/R | 0.3239 | likely_benign | 0.3215 | benign | -0.517 | Destabilizing | 0.935 | D | 0.613 | neutral | N | 0.496951523 | None | None | N |
| T/S | 0.1172 | likely_benign | 0.1064 | benign | -1.098 | Destabilizing | 0.099 | N | 0.495 | neutral | N | 0.435534918 | None | None | N |
| T/V | 0.183 | likely_benign | 0.1812 | benign | -0.229 | Destabilizing | 0.916 | D | 0.505 | neutral | None | None | None | None | N |
| T/W | 0.821 | likely_pathogenic | 0.7885 | pathogenic | -0.742 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | N |
| T/Y | 0.4719 | ambiguous | 0.4401 | ambiguous | -0.404 | Destabilizing | 0.996 | D | 0.73 | prob.delet. | 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.