Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7657 | 23194;23195;23196 | chr2:178721050;178721049;178721048 | chr2:179585777;179585776;179585775 |
| N2AB | 7340 | 22243;22244;22245 | chr2:178721050;178721049;178721048 | chr2:179585777;179585776;179585775 |
| N2A | 6413 | 19462;19463;19464 | chr2:178721050;178721049;178721048 | chr2:179585777;179585776;179585775 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/I | rs749090360  |
-0.544 | 0.057 | N | 0.286 | 0.249 | 0.52540932818 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 6.47E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| M/I | rs749090360 |
-0.544 | 0.057 | N | 0.286 | 0.249 | 0.52540932818 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06782E-04 | 0 |
| M/I | rs749090360 |
-0.544 | 0.057 | N | 0.286 | 0.249 | 0.52540932818 | gnomAD-4.0.0 | 4.95896E-06 | None | None | None | None | I | None | 1.33522E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54362E-06 | 4.39309E-05 | 0 |
| M/T | rs770782245 |
-0.601 | 0.324 | N | 0.376 | 0.372 | 0.667668966213 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/T | rs770782245 |
-0.601 | 0.324 | N | 0.376 | 0.372 | 0.667668966213 | gnomAD-4.0.0 | 2.73763E-06 | None | None | None | None | I | None | 0 | 6.70931E-05 | None | 0 | 0 | None | 0 | 0 | 8.9974E-07 | 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 | 0.5516 | ambiguous | 0.555 | ambiguous | -2.024 | Highly Destabilizing | 0.304 | N | 0.313 | neutral | None | None | None | None | I |
| M/C | 0.8531 | likely_pathogenic | 0.8453 | pathogenic | -1.599 | Destabilizing | 0.979 | D | 0.442 | neutral | None | None | None | None | I |
| M/D | 0.9416 | likely_pathogenic | 0.949 | pathogenic | -0.806 | Destabilizing | 0.69 | D | 0.549 | neutral | None | None | None | None | I |
| M/E | 0.7282 | likely_pathogenic | 0.7529 | pathogenic | -0.727 | Destabilizing | 0.114 | N | 0.422 | neutral | None | None | None | None | I |
| M/F | 0.3648 | ambiguous | 0.3903 | ambiguous | -0.932 | Destabilizing | 0.09 | N | 0.415 | neutral | None | None | None | None | I |
| M/G | 0.8181 | likely_pathogenic | 0.8172 | pathogenic | -2.398 | Highly Destabilizing | 0.811 | D | 0.48 | neutral | None | None | None | None | I |
| M/H | 0.6568 | likely_pathogenic | 0.6805 | pathogenic | -1.552 | Destabilizing | 0.862 | D | 0.473 | neutral | None | None | None | None | I |
| M/I | 0.4008 | ambiguous | 0.4184 | ambiguous | -1.024 | Destabilizing | 0.057 | N | 0.286 | neutral | N | 0.432007116 | None | None | I |
| M/K | 0.2668 | likely_benign | 0.275 | benign | -0.705 | Destabilizing | 0.129 | N | 0.369 | neutral | N | 0.486328347 | None | None | I |
| M/L | 0.2099 | likely_benign | 0.1964 | benign | -1.024 | Destabilizing | None | N | 0.085 | neutral | N | 0.456654844 | None | None | I |
| M/N | 0.7466 | likely_pathogenic | 0.7647 | pathogenic | -0.671 | Destabilizing | 0.819 | D | 0.501 | neutral | None | None | None | None | I |
| M/P | 0.9311 | likely_pathogenic | 0.9409 | pathogenic | -1.332 | Destabilizing | 0.932 | D | 0.505 | neutral | None | None | None | None | I |
| M/Q | 0.3531 | ambiguous | 0.3794 | ambiguous | -0.666 | Destabilizing | 0.033 | N | 0.228 | neutral | None | None | None | None | I |
| M/R | 0.2885 | likely_benign | 0.3004 | benign | -0.396 | Destabilizing | 0.388 | N | 0.468 | neutral | N | 0.48789851 | None | None | I |
| M/S | 0.5941 | likely_pathogenic | 0.6019 | pathogenic | -1.343 | Destabilizing | 0.679 | D | 0.365 | neutral | None | None | None | None | I |
| M/T | 0.3723 | ambiguous | 0.3624 | ambiguous | -1.137 | Destabilizing | 0.324 | N | 0.376 | neutral | N | 0.478224982 | None | None | I |
| M/V | 0.1283 | likely_benign | 0.1246 | benign | -1.332 | Destabilizing | 0.001 | N | 0.111 | neutral | N | 0.486665533 | None | None | I |
| M/W | 0.7725 | likely_pathogenic | 0.8014 | pathogenic | -0.911 | Destabilizing | 0.996 | D | 0.447 | neutral | None | None | None | None | I |
| M/Y | 0.6791 | likely_pathogenic | 0.713 | pathogenic | -0.928 | Destabilizing | 0.893 | D | 0.462 | 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.