Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7641 | 23146;23147;23148 | chr2:178721098;178721097;178721096 | chr2:179585825;179585824;179585823 |
| N2AB | 7324 | 22195;22196;22197 | chr2:178721098;178721097;178721096 | chr2:179585825;179585824;179585823 |
| N2A | 6397 | 19414;19415;19416 | chr2:178721098;178721097;178721096 | chr2:179585825;179585824;179585823 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/L | rs369508943  |
0.579 | None | D | 0.299 | 0.152 | None | gnomAD-2.1.1 | 5.36E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.09582E-04 | 1.40687E-04 |
| S/L | rs369508943 |
0.579 | None | D | 0.299 | 0.152 | None | gnomAD-3.1.2 | 5.91E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.02911E-04 | 0 | 0 |
| S/L | rs369508943 |
0.579 | None | D | 0.299 | 0.152 | None | gnomAD-4.0.0 | 7.12877E-05 | None | None | None | None | N | None | 2.67073E-05 | 0 | None | 0 | 0 | None | 1.56245E-05 | 0 | 9.24216E-05 | 0 | 4.80554E-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 | 0.0702 | likely_benign | 0.0743 | benign | -0.58 | Destabilizing | None | N | 0.207 | neutral | N | 0.51082019 | None | None | N |
| S/C | 0.1452 | likely_benign | 0.1095 | benign | -0.234 | Destabilizing | 0.132 | N | 0.509 | neutral | None | None | None | None | N |
| S/D | 0.271 | likely_benign | 0.335 | benign | -0.953 | Destabilizing | 0.004 | N | 0.42 | neutral | None | None | None | None | N |
| S/E | 0.2811 | likely_benign | 0.4101 | ambiguous | -0.82 | Destabilizing | 0.002 | N | 0.397 | neutral | None | None | None | None | N |
| S/F | 0.1114 | likely_benign | 0.148 | benign | -0.328 | Destabilizing | 0.004 | N | 0.499 | neutral | None | None | None | None | N |
| S/G | 0.1269 | likely_benign | 0.1105 | benign | -0.955 | Destabilizing | 0.002 | N | 0.417 | neutral | None | None | None | None | N |
| S/H | 0.1629 | likely_benign | 0.2183 | benign | -1.417 | Destabilizing | 0.069 | N | 0.545 | neutral | None | None | None | None | N |
| S/I | 0.0793 | likely_benign | 0.0966 | benign | 0.356 | Stabilizing | 0.001 | N | 0.473 | neutral | None | None | None | None | N |
| S/K | 0.2352 | likely_benign | 0.3811 | ambiguous | -0.549 | Destabilizing | 0.002 | N | 0.395 | neutral | None | None | None | None | N |
| S/L | 0.0611 | likely_benign | 0.0823 | benign | 0.356 | Stabilizing | None | N | 0.299 | neutral | D | 0.526040358 | None | None | N |
| S/M | 0.096 | likely_benign | 0.1185 | benign | 0.411 | Stabilizing | None | N | 0.291 | neutral | None | None | None | None | N |
| S/N | 0.114 | likely_benign | 0.1114 | benign | -0.919 | Destabilizing | None | N | 0.26 | neutral | None | None | None | None | N |
| S/P | 0.7829 | likely_pathogenic | 0.8674 | pathogenic | 0.08 | Stabilizing | 0.013 | N | 0.502 | neutral | D | 0.537139301 | None | None | N |
| S/Q | 0.2088 | likely_benign | 0.3139 | benign | -0.733 | Destabilizing | None | N | 0.285 | neutral | None | None | None | None | N |
| S/R | 0.1822 | likely_benign | 0.2896 | benign | -0.823 | Destabilizing | 0.004 | N | 0.483 | neutral | None | None | None | None | N |
| S/T | 0.0662 | likely_benign | 0.0689 | benign | -0.663 | Destabilizing | None | N | 0.195 | neutral | N | 0.450963809 | None | None | N |
| S/V | 0.075 | likely_benign | 0.0911 | benign | 0.08 | Stabilizing | None | N | 0.321 | neutral | None | None | None | None | N |
| S/W | 0.1836 | likely_benign | 0.2459 | benign | -0.605 | Destabilizing | 0.132 | N | 0.557 | neutral | None | None | None | None | N |
| S/Y | 0.1228 | likely_benign | 0.1468 | benign | -0.213 | Destabilizing | None | N | 0.337 | 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.