Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15225 | 45898;45899;45900 | chr2:178620937;178620936;178620935 | chr2:179485664;179485663;179485662 |
| N2AB | 13584 | 40975;40976;40977 | chr2:178620937;178620936;178620935 | chr2:179485664;179485663;179485662 |
| N2A | 12657 | 38194;38195;38196 | chr2:178620937;178620936;178620935 | chr2:179485664;179485663;179485662 |
| N2B | 6160 | 18703;18704;18705 | chr2:178620937;178620936;178620935 | chr2:179485664;179485663;179485662 |
| Novex-1 | 6285 | 19078;19079;19080 | chr2:178620937;178620936;178620935 | chr2:179485664;179485663;179485662 |
| Novex-2 | 6352 | 19279;19280;19281 | chr2:178620937;178620936;178620935 | chr2:179485664;179485663;179485662 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1449233780  |
-2.17 | 0.001 | N | 0.201 | 0.079 | 0.199424873507 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs1449233780 |
-2.17 | 0.001 | N | 0.201 | 0.079 | 0.199424873507 | gnomAD-4.0.0 | 1.59415E-06 | None | None | None | None | N | None | 5.67795E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/F | None | None | 0.655 | N | 0.725 | 0.213 | 0.677595378676 | gnomAD-4.0.0 | 6.84749E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99883E-07 | 0 | 0 |
| V/I | rs757519339 |
-0.292 | 0.001 | N | 0.236 | 0.081 | 0.324986149311 | gnomAD-2.1.1 | 8.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| V/I | rs757519339 |
-0.292 | 0.001 | N | 0.236 | 0.081 | 0.324986149311 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs757519339 |
-0.292 | 0.001 | N | 0.236 | 0.081 | 0.324986149311 | gnomAD-4.0.0 | 1.24047E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69612E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.212 | likely_benign | 0.1652 | benign | -1.745 | Destabilizing | 0.001 | N | 0.201 | neutral | N | 0.448805238 | None | None | N |
| V/C | 0.8589 | likely_pathogenic | 0.7979 | pathogenic | -1.331 | Destabilizing | 0.951 | D | 0.681 | prob.neutral | None | None | None | None | N |
| V/D | 0.9414 | likely_pathogenic | 0.8803 | pathogenic | -1.86 | Destabilizing | 0.655 | D | 0.737 | prob.delet. | N | 0.503886857 | None | None | N |
| V/E | 0.8906 | likely_pathogenic | 0.8231 | pathogenic | -1.71 | Destabilizing | 0.418 | N | 0.685 | prob.neutral | None | None | None | None | N |
| V/F | 0.5392 | ambiguous | 0.4801 | ambiguous | -1.011 | Destabilizing | 0.655 | D | 0.725 | prob.delet. | N | 0.478290441 | None | None | N |
| V/G | 0.5544 | ambiguous | 0.4213 | ambiguous | -2.22 | Highly Destabilizing | 0.001 | N | 0.503 | neutral | N | 0.457821173 | None | None | N |
| V/H | 0.9637 | likely_pathogenic | 0.9309 | pathogenic | -1.779 | Destabilizing | 0.983 | D | 0.7 | prob.neutral | None | None | None | None | N |
| V/I | 0.11 | likely_benign | 0.1189 | benign | -0.469 | Destabilizing | 0.001 | N | 0.236 | neutral | N | 0.447901246 | None | None | N |
| V/K | 0.9201 | likely_pathogenic | 0.8487 | pathogenic | -1.595 | Destabilizing | 0.418 | N | 0.685 | prob.neutral | None | None | None | None | N |
| V/L | 0.4844 | ambiguous | 0.4584 | ambiguous | -0.469 | Destabilizing | 0.001 | N | 0.249 | neutral | N | 0.457662966 | None | None | N |
| V/M | 0.3493 | ambiguous | 0.3433 | ambiguous | -0.475 | Destabilizing | 0.716 | D | 0.632 | neutral | None | None | None | None | N |
| V/N | 0.87 | likely_pathogenic | 0.7732 | pathogenic | -1.718 | Destabilizing | 0.716 | D | 0.744 | deleterious | None | None | None | None | N |
| V/P | 0.976 | likely_pathogenic | 0.9457 | pathogenic | -0.862 | Destabilizing | 0.836 | D | 0.723 | prob.delet. | None | None | None | None | N |
| V/Q | 0.8968 | likely_pathogenic | 0.8272 | pathogenic | -1.657 | Destabilizing | 0.836 | D | 0.713 | prob.delet. | None | None | None | None | N |
| V/R | 0.8841 | likely_pathogenic | 0.7903 | pathogenic | -1.29 | Destabilizing | 0.716 | D | 0.735 | prob.delet. | None | None | None | None | N |
| V/S | 0.5917 | likely_pathogenic | 0.464 | ambiguous | -2.343 | Highly Destabilizing | 0.264 | N | 0.617 | neutral | None | None | None | None | N |
| V/T | 0.3342 | likely_benign | 0.2652 | benign | -2.05 | Highly Destabilizing | 0.01 | N | 0.321 | neutral | None | None | None | None | N |
| V/W | 0.9787 | likely_pathogenic | 0.963 | pathogenic | -1.393 | Destabilizing | 0.983 | D | 0.703 | prob.neutral | None | None | None | None | N |
| V/Y | 0.9131 | likely_pathogenic | 0.8573 | pathogenic | -1.021 | Destabilizing | 0.836 | D | 0.715 | 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.