Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28347 | 85264;85265;85266 | chr2:178561093;178561092;178561091 | chr2:179425820;179425819;179425818 |
| N2AB | 26706 | 80341;80342;80343 | chr2:178561093;178561092;178561091 | chr2:179425820;179425819;179425818 |
| N2A | 25779 | 77560;77561;77562 | chr2:178561093;178561092;178561091 | chr2:179425820;179425819;179425818 |
| N2B | 19282 | 58069;58070;58071 | chr2:178561093;178561092;178561091 | chr2:179425820;179425819;179425818 |
| Novex-1 | 19407 | 58444;58445;58446 | chr2:178561093;178561092;178561091 | chr2:179425820;179425819;179425818 |
| Novex-2 | 19474 | 58645;58646;58647 | chr2:178561093;178561092;178561091 | chr2:179425820;179425819;179425818 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/R | rs397517731  |
-0.352 | 0.016 | N | 0.605 | 0.166 | 0.531727546574 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/R | rs397517731 |
-0.352 | 0.016 | N | 0.605 | 0.166 | 0.531727546574 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 1.31062E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/R | rs397517731 |
-0.352 | 0.016 | N | 0.605 | 0.166 | 0.531727546574 | gnomAD-4.0.0 | 1.85899E-06 | None | None | None | None | N | None | 0 | 5.00167E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs397517731 |
-1.42 | None | N | 0.104 | 0.148 | 0.396494342077 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 1.65782E-04 |
| I/T | rs397517731 |
-1.42 | None | N | 0.104 | 0.148 | 0.396494342077 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs397517731 |
-1.42 | None | N | 0.104 | 0.148 | 0.396494342077 | gnomAD-4.0.0 | 2.04489E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.79701E-05 | 0 | 0 |
| I/V | rs1553563774 |
None | 0.001 | N | 0.148 | 0.148 | 0.341226946553 | gnomAD-4.0.0 | 2.05256E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69834E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.143 | likely_benign | 0.1378 | benign | -1.474 | Destabilizing | 0.001 | N | 0.311 | neutral | None | None | None | None | N |
| I/C | 0.4974 | ambiguous | 0.5736 | pathogenic | -0.864 | Destabilizing | 0.131 | N | 0.288 | neutral | None | None | None | None | N |
| I/D | 0.5554 | ambiguous | 0.5707 | pathogenic | -0.988 | Destabilizing | 0.009 | N | 0.487 | neutral | None | None | None | None | N |
| I/E | 0.4404 | ambiguous | 0.4677 | ambiguous | -0.989 | Destabilizing | 0.009 | N | 0.403 | neutral | None | None | None | None | N |
| I/F | 0.1693 | likely_benign | 0.1892 | benign | -0.965 | Destabilizing | 0.021 | N | 0.262 | neutral | None | None | None | None | N |
| I/G | 0.5289 | ambiguous | 0.5218 | ambiguous | -1.784 | Destabilizing | 0.009 | N | 0.418 | neutral | None | None | None | None | N |
| I/H | 0.3404 | ambiguous | 0.3986 | ambiguous | -0.908 | Destabilizing | 0.314 | N | 0.431 | neutral | None | None | None | None | N |
| I/K | 0.2925 | likely_benign | 0.3308 | benign | -1.083 | Destabilizing | 0.007 | N | 0.402 | neutral | N | 0.435764205 | None | None | N |
| I/L | 0.096 | likely_benign | 0.1073 | benign | -0.701 | Destabilizing | None | N | 0.039 | neutral | N | 0.419986676 | None | None | N |
| I/M | 0.077 | likely_benign | 0.0833 | benign | -0.56 | Destabilizing | 0.053 | N | 0.368 | neutral | N | 0.473898518 | None | None | N |
| I/N | 0.1869 | likely_benign | 0.1944 | benign | -0.923 | Destabilizing | 0.009 | N | 0.499 | neutral | None | None | None | None | N |
| I/P | 0.5129 | ambiguous | 0.4968 | ambiguous | -0.927 | Destabilizing | 0.041 | N | 0.594 | neutral | None | None | None | None | N |
| I/Q | 0.2928 | likely_benign | 0.3286 | benign | -1.095 | Destabilizing | 0.041 | N | 0.653 | prob.neutral | None | None | None | None | N |
| I/R | 0.2042 | likely_benign | 0.2324 | benign | -0.444 | Destabilizing | 0.016 | N | 0.605 | neutral | N | 0.446807918 | None | None | N |
| I/S | 0.1472 | likely_benign | 0.1455 | benign | -1.491 | Destabilizing | 0.002 | N | 0.317 | neutral | None | None | None | None | N |
| I/T | 0.0501 | likely_benign | 0.0504 | benign | -1.378 | Destabilizing | None | N | 0.104 | neutral | N | 0.351337454 | None | None | N |
| I/V | 0.0657 | likely_benign | 0.0658 | benign | -0.927 | Destabilizing | 0.001 | N | 0.148 | neutral | N | 0.41227127 | None | None | N |
| I/W | 0.6505 | likely_pathogenic | 0.7039 | pathogenic | -1.037 | Destabilizing | 0.633 | D | 0.432 | neutral | None | None | None | None | N |
| I/Y | 0.3998 | ambiguous | 0.4424 | ambiguous | -0.825 | Destabilizing | 0.041 | N | 0.543 | 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.