Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30729 | 92410;92411;92412 | chr2:178549441;178549440;178549439 | chr2:179414168;179414167;179414166 |
| N2AB | 29088 | 87487;87488;87489 | chr2:178549441;178549440;178549439 | chr2:179414168;179414167;179414166 |
| N2A | 28161 | 84706;84707;84708 | chr2:178549441;178549440;178549439 | chr2:179414168;179414167;179414166 |
| N2B | 21664 | 65215;65216;65217 | chr2:178549441;178549440;178549439 | chr2:179414168;179414167;179414166 |
| Novex-1 | 21789 | 65590;65591;65592 | chr2:178549441;178549440;178549439 | chr2:179414168;179414167;179414166 |
| Novex-2 | 21856 | 65791;65792;65793 | chr2:178549441;178549440;178549439 | chr2:179414168;179414167;179414166 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/R | rs778827102  |
0.099 | 0.901 | N | 0.543 | 0.269 | 0.324161360171 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/R | rs778827102 |
0.099 | 0.901 | N | 0.543 | 0.269 | 0.324161360171 | gnomAD-4.0.0 | 3.19993E-06 | None | None | None | None | N | None | 5.70386E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.03711E-05 |
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 | 0.0917 | likely_benign | 0.101 | benign | -0.529 | Destabilizing | 0.415 | N | 0.316 | neutral | None | None | None | None | N |
| S/C | 0.1142 | likely_benign | 0.1251 | benign | -0.419 | Destabilizing | 0.995 | D | 0.561 | neutral | N | 0.518023016 | None | None | N |
| S/D | 0.5431 | ambiguous | 0.6464 | pathogenic | -0.074 | Destabilizing | 0.775 | D | 0.503 | neutral | None | None | None | None | N |
| S/E | 0.6498 | likely_pathogenic | 0.7237 | pathogenic | -0.135 | Destabilizing | 0.775 | D | 0.492 | neutral | None | None | None | None | N |
| S/F | 0.2742 | likely_benign | 0.3525 | ambiguous | -0.952 | Destabilizing | 0.961 | D | 0.624 | neutral | None | None | None | None | N |
| S/G | 0.1006 | likely_benign | 0.118 | benign | -0.702 | Destabilizing | 0.722 | D | 0.521 | neutral | N | 0.479476768 | None | None | N |
| S/H | 0.47 | ambiguous | 0.5337 | ambiguous | -1.245 | Destabilizing | 0.996 | D | 0.561 | neutral | None | None | None | None | N |
| S/I | 0.2225 | likely_benign | 0.2659 | benign | -0.194 | Destabilizing | 0.82 | D | 0.545 | neutral | N | 0.498858465 | None | None | N |
| S/K | 0.8014 | likely_pathogenic | 0.857 | pathogenic | -0.651 | Destabilizing | 0.775 | D | 0.502 | neutral | None | None | None | None | N |
| S/L | 0.1264 | likely_benign | 0.1547 | benign | -0.194 | Destabilizing | 0.633 | D | 0.545 | neutral | None | None | None | None | N |
| S/M | 0.2163 | likely_benign | 0.2431 | benign | 0.08 | Stabilizing | 0.989 | D | 0.565 | neutral | None | None | None | None | N |
| S/N | 0.1856 | likely_benign | 0.2294 | benign | -0.471 | Destabilizing | 0.722 | D | 0.527 | neutral | N | 0.5016824 | None | None | N |
| S/P | 0.8837 | likely_pathogenic | 0.9333 | pathogenic | -0.274 | Destabilizing | 0.961 | D | 0.544 | neutral | None | None | None | None | N |
| S/Q | 0.5876 | likely_pathogenic | 0.6362 | pathogenic | -0.7 | Destabilizing | 0.961 | D | 0.55 | neutral | None | None | None | None | N |
| S/R | 0.7384 | likely_pathogenic | 0.8099 | pathogenic | -0.467 | Destabilizing | 0.901 | D | 0.543 | neutral | N | 0.485691286 | None | None | N |
| S/T | 0.0764 | likely_benign | 0.0821 | benign | -0.529 | Destabilizing | 0.001 | N | 0.109 | neutral | N | 0.41597051 | None | None | N |
| S/V | 0.1762 | likely_benign | 0.2157 | benign | -0.274 | Destabilizing | 0.633 | D | 0.543 | neutral | None | None | None | None | N |
| S/W | 0.4697 | ambiguous | 0.5574 | ambiguous | -0.928 | Destabilizing | 0.996 | D | 0.697 | prob.neutral | None | None | None | None | N |
| S/Y | 0.2873 | likely_benign | 0.3478 | ambiguous | -0.664 | Destabilizing | 0.961 | D | 0.62 | neutral | 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.