Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20921 | 62986;62987;62988 | chr2:178588964;178588963;178588962 | chr2:179453691;179453690;179453689 |
| N2AB | 19280 | 58063;58064;58065 | chr2:178588964;178588963;178588962 | chr2:179453691;179453690;179453689 |
| N2A | 18353 | 55282;55283;55284 | chr2:178588964;178588963;178588962 | chr2:179453691;179453690;179453689 |
| N2B | 11856 | 35791;35792;35793 | chr2:178588964;178588963;178588962 | chr2:179453691;179453690;179453689 |
| Novex-1 | 11981 | 36166;36167;36168 | chr2:178588964;178588963;178588962 | chr2:179453691;179453690;179453689 |
| Novex-2 | 12048 | 36367;36368;36369 | chr2:178588964;178588963;178588962 | chr2:179453691;179453690;179453689 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/R | rs2154183465  |
None | 0.968 | N | 0.605 | 0.215 | 0.3349148499 | gnomAD-4.0.0 | 3.18856E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58722E-05 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs935268567 |
None | 0.811 | N | 0.485 | 0.081 | 0.242244723065 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/S | rs935268567 |
None | 0.811 | N | 0.485 | 0.081 | 0.242244723065 | gnomAD-4.0.0 | 1.86062E-06 | None | None | None | None | N | None | 1.33568E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.6958E-06 | 0 | 0 |
| P/T | None | -1.559 | 0.103 | N | 0.348 | 0.067 | 0.146414634003 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14732E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/T | None | -1.559 | 0.103 | N | 0.348 | 0.067 | 0.146414634003 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.79846E-04 |
| P/T | None | -1.559 | 0.103 | N | 0.348 | 0.067 | 0.146414634003 | gnomAD-4.0.0 | 5.58187E-06 | None | None | None | None | N | None | 1.33568E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47902E-07 | 0 | 1.12197E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0698 | likely_benign | 0.0675 | benign | -1.39 | Destabilizing | 0.811 | D | 0.479 | neutral | N | 0.488385181 | None | None | N |
| P/C | 0.3036 | likely_benign | 0.2709 | benign | -0.875 | Destabilizing | 0.999 | D | 0.72 | prob.delet. | None | None | None | None | N |
| P/D | 0.4838 | ambiguous | 0.4954 | ambiguous | -1.22 | Destabilizing | 0.851 | D | 0.459 | neutral | None | None | None | None | N |
| P/E | 0.3219 | likely_benign | 0.3287 | benign | -1.122 | Destabilizing | 0.919 | D | 0.47 | neutral | None | None | None | None | N |
| P/F | 0.5267 | ambiguous | 0.5299 | ambiguous | -0.896 | Destabilizing | 0.988 | D | 0.699 | prob.neutral | None | None | None | None | N |
| P/G | 0.2345 | likely_benign | 0.2264 | benign | -1.786 | Destabilizing | 0.851 | D | 0.545 | neutral | None | None | None | None | N |
| P/H | 0.1928 | likely_benign | 0.1872 | benign | -1.26 | Destabilizing | 0.984 | D | 0.66 | neutral | N | 0.512262119 | None | None | N |
| P/I | 0.3415 | ambiguous | 0.3432 | ambiguous | -0.365 | Destabilizing | 0.976 | D | 0.667 | neutral | None | None | None | None | N |
| P/K | 0.2611 | likely_benign | 0.2511 | benign | -1.069 | Destabilizing | 0.919 | D | 0.483 | neutral | None | None | None | None | N |
| P/L | 0.1249 | likely_benign | 0.1206 | benign | -0.365 | Destabilizing | 0.811 | D | 0.601 | neutral | N | 0.426219215 | None | None | N |
| P/M | 0.2783 | likely_benign | 0.2779 | benign | -0.362 | Destabilizing | 0.999 | D | 0.661 | neutral | None | None | None | None | N |
| P/N | 0.2522 | likely_benign | 0.2374 | benign | -1.102 | Destabilizing | 0.015 | N | 0.423 | neutral | None | None | None | None | N |
| P/Q | 0.1545 | likely_benign | 0.1464 | benign | -1.107 | Destabilizing | 0.988 | D | 0.575 | neutral | None | None | None | None | N |
| P/R | 0.174 | likely_benign | 0.1612 | benign | -0.742 | Destabilizing | 0.968 | D | 0.605 | neutral | N | 0.448191997 | None | None | N |
| P/S | 0.1152 | likely_benign | 0.1092 | benign | -1.677 | Destabilizing | 0.811 | D | 0.485 | neutral | N | 0.492886924 | None | None | N |
| P/T | 0.0875 | likely_benign | 0.0848 | benign | -1.445 | Destabilizing | 0.103 | N | 0.348 | neutral | N | 0.394277368 | None | None | N |
| P/V | 0.2057 | likely_benign | 0.2103 | benign | -0.674 | Destabilizing | 0.851 | D | 0.569 | neutral | None | None | None | None | N |
| P/W | 0.6365 | likely_pathogenic | 0.6569 | pathogenic | -1.193 | Destabilizing | 0.999 | D | 0.719 | prob.delet. | None | None | None | None | N |
| P/Y | 0.4126 | ambiguous | 0.4193 | ambiguous | -0.813 | Destabilizing | 0.996 | D | 0.699 | prob.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.