Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16011 | 48256;48257;48258 | chr2:178616858;178616857;178616856 | chr2:179481585;179481584;179481583 |
| N2AB | 14370 | 43333;43334;43335 | chr2:178616858;178616857;178616856 | chr2:179481585;179481584;179481583 |
| N2A | 13443 | 40552;40553;40554 | chr2:178616858;178616857;178616856 | chr2:179481585;179481584;179481583 |
| N2B | 6946 | 21061;21062;21063 | chr2:178616858;178616857;178616856 | chr2:179481585;179481584;179481583 |
| Novex-1 | 7071 | 21436;21437;21438 | chr2:178616858;178616857;178616856 | chr2:179481585;179481584;179481583 |
| Novex-2 | 7138 | 21637;21638;21639 | chr2:178616858;178616857;178616856 | chr2:179481585;179481584;179481583 |
| 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 | rs754476448  |
-0.572 | 0.662 | N | 0.543 | 0.422 | 0.659656470797 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| M/K | rs754476448 |
-0.572 | 0.662 | N | 0.543 | 0.422 | 0.659656470797 | gnomAD-4.0.0 | 1.59342E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43316E-05 | 0 |
| M/L | rs2057430737 |
None | 0.001 | N | 0.095 | 0.151 | 0.512424132817 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/L | rs2057430737 |
None | 0.001 | N | 0.095 | 0.151 | 0.512424132817 | gnomAD-4.0.0 | 6.58432E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47284E-05 | 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 | 0.5971 | likely_pathogenic | 0.5971 | pathogenic | -1.89 | Destabilizing | 0.345 | N | 0.351 | neutral | None | None | None | None | I |
| M/C | 0.7418 | likely_pathogenic | 0.7312 | pathogenic | -1.453 | Destabilizing | 0.965 | D | 0.527 | neutral | None | None | None | None | I |
| M/D | 0.9337 | likely_pathogenic | 0.9265 | pathogenic | -0.772 | Destabilizing | 0.965 | D | 0.625 | neutral | None | None | None | None | I |
| M/E | 0.6259 | likely_pathogenic | 0.6201 | pathogenic | -0.688 | Destabilizing | 0.888 | D | 0.609 | neutral | None | None | None | None | I |
| M/F | 0.4793 | ambiguous | 0.4267 | ambiguous | -0.685 | Destabilizing | 0.561 | D | 0.489 | neutral | None | None | None | None | I |
| M/G | 0.7943 | likely_pathogenic | 0.786 | pathogenic | -2.259 | Highly Destabilizing | 0.722 | D | 0.589 | neutral | None | None | None | None | I |
| M/H | 0.7464 | likely_pathogenic | 0.7247 | pathogenic | -1.394 | Destabilizing | 0.991 | D | 0.553 | neutral | None | None | None | None | I |
| M/I | 0.3108 | likely_benign | 0.2696 | benign | -0.902 | Destabilizing | 0.001 | N | 0.086 | neutral | N | 0.447600991 | None | None | I |
| M/K | 0.3215 | likely_benign | 0.3202 | benign | -0.804 | Destabilizing | 0.662 | D | 0.543 | neutral | N | 0.512069009 | None | None | I |
| M/L | 0.1732 | likely_benign | 0.1765 | benign | -0.902 | Destabilizing | 0.001 | N | 0.095 | neutral | N | 0.481738075 | None | None | I |
| M/N | 0.7145 | likely_pathogenic | 0.6828 | pathogenic | -0.789 | Destabilizing | 0.965 | D | 0.593 | neutral | None | None | None | None | I |
| M/P | 0.9195 | likely_pathogenic | 0.9097 | pathogenic | -1.205 | Destabilizing | 0.965 | D | 0.593 | neutral | None | None | None | None | I |
| M/Q | 0.3484 | ambiguous | 0.3309 | benign | -0.762 | Destabilizing | 0.965 | D | 0.515 | neutral | None | None | None | None | I |
| M/R | 0.3679 | ambiguous | 0.3752 | ambiguous | -0.442 | Destabilizing | 0.954 | D | 0.581 | neutral | D | 0.570730881 | None | None | I |
| M/S | 0.642 | likely_pathogenic | 0.633 | pathogenic | -1.414 | Destabilizing | 0.722 | D | 0.473 | neutral | None | None | None | None | I |
| M/T | 0.3496 | ambiguous | 0.3595 | ambiguous | -1.21 | Destabilizing | 0.491 | N | 0.47 | neutral | D | 0.568387262 | None | None | I |
| M/V | 0.1255 | likely_benign | 0.1273 | benign | -1.205 | Destabilizing | 0.005 | N | 0.107 | neutral | N | 0.483892158 | None | None | I |
| M/W | 0.7672 | likely_pathogenic | 0.7198 | pathogenic | -0.699 | Destabilizing | 0.991 | D | 0.529 | neutral | None | None | None | None | I |
| M/Y | 0.6914 | likely_pathogenic | 0.6525 | pathogenic | -0.729 | Destabilizing | 0.901 | D | 0.577 | neutral | None | None | 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.