Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2289 | 7090;7091;7092 | chr2:178774399;178774398;178774397 | chr2:179639126;179639125;179639124 |
| N2AB | 2289 | 7090;7091;7092 | chr2:178774399;178774398;178774397 | chr2:179639126;179639125;179639124 |
| N2A | 2289 | 7090;7091;7092 | chr2:178774399;178774398;178774397 | chr2:179639126;179639125;179639124 |
| N2B | 2243 | 6952;6953;6954 | chr2:178774399;178774398;178774397 | chr2:179639126;179639125;179639124 |
| Novex-1 | 2243 | 6952;6953;6954 | chr2:178774399;178774398;178774397 | chr2:179639126;179639125;179639124 |
| Novex-2 | 2243 | 6952;6953;6954 | chr2:178774399;178774398;178774397 | chr2:179639126;179639125;179639124 |
| Novex-3 | 2289 | 7090;7091;7092 | chr2:178774399;178774398;178774397 | chr2:179639126;179639125;179639124 |
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/F | None | None | 0.171 | N | 0.51 | 0.186 | 0.346544149963 | gnomAD-4.0.0 | 3.18184E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71386E-06 | 0 | 0 |
| I/S | rs200440412  |
-1.47 | 0.024 | N | 0.529 | 0.24 | None | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.65E-05 | 0 |
| I/S | rs200440412 |
-1.47 | 0.024 | N | 0.529 | 0.24 | None | gnomAD-4.0.0 | 2.5998E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.14775E-05 | 0 | 4.96771E-05 |
| I/V | rs1274078547 |
None | None | N | 0.129 | 0.089 | 0.435915822735 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs1274078547 |
None | None | N | 0.129 | 0.089 | 0.435915822735 | gnomAD-4.0.0 | 3.84226E-06 | None | None | None | None | N | None | 1.69062E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78396E-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 | 0.1622 | likely_benign | 0.1612 | benign | -2.131 | Highly Destabilizing | 0.007 | N | 0.316 | neutral | None | None | None | None | N |
| I/C | 0.5922 | likely_pathogenic | 0.5907 | pathogenic | -1.419 | Destabilizing | 0.676 | D | 0.527 | neutral | None | None | None | None | N |
| I/D | 0.4383 | ambiguous | 0.4338 | ambiguous | -1.939 | Destabilizing | 0.016 | N | 0.513 | neutral | None | None | None | None | N |
| I/E | 0.2204 | likely_benign | 0.2231 | benign | -1.892 | Destabilizing | None | N | 0.341 | neutral | None | None | None | None | N |
| I/F | 0.1409 | likely_benign | 0.1402 | benign | -1.48 | Destabilizing | 0.171 | N | 0.51 | neutral | N | 0.453310733 | None | None | N |
| I/G | 0.5101 | ambiguous | 0.502 | ambiguous | -2.495 | Highly Destabilizing | 0.072 | N | 0.583 | neutral | None | None | None | None | N |
| I/H | 0.3466 | ambiguous | 0.3431 | ambiguous | -1.639 | Destabilizing | 0.356 | N | 0.6 | neutral | None | None | None | None | N |
| I/K | 0.2753 | likely_benign | 0.2726 | benign | -1.475 | Destabilizing | 0.016 | N | 0.537 | neutral | None | None | None | None | N |
| I/L | 0.1123 | likely_benign | 0.11 | benign | -1.165 | Destabilizing | 0.005 | N | 0.223 | neutral | N | 0.474924225 | None | None | N |
| I/M | 0.0867 | likely_benign | 0.0862 | benign | -0.961 | Destabilizing | 0.171 | N | 0.509 | neutral | N | 0.485490454 | None | None | N |
| I/N | 0.1787 | likely_benign | 0.1763 | benign | -1.403 | Destabilizing | 0.055 | N | 0.622 | neutral | N | 0.482908036 | None | None | N |
| I/P | 0.8894 | likely_pathogenic | 0.8714 | pathogenic | -1.46 | Destabilizing | 0.136 | N | 0.631 | neutral | None | None | None | None | N |
| I/Q | 0.2453 | likely_benign | 0.2442 | benign | -1.578 | Destabilizing | 0.038 | N | 0.601 | neutral | None | None | None | None | N |
| I/R | 0.2244 | likely_benign | 0.2227 | benign | -0.851 | Destabilizing | 0.072 | N | 0.626 | neutral | None | None | None | None | N |
| I/S | 0.1543 | likely_benign | 0.1542 | benign | -2.052 | Highly Destabilizing | 0.024 | N | 0.529 | neutral | N | 0.4962029 | None | None | N |
| I/T | 0.0827 | likely_benign | 0.0837 | benign | -1.893 | Destabilizing | 0.012 | N | 0.494 | neutral | N | 0.432911749 | None | None | N |
| I/V | 0.063 | likely_benign | 0.0638 | benign | -1.46 | Destabilizing | None | N | 0.129 | neutral | N | 0.439339738 | None | None | N |
| I/W | 0.706 | likely_pathogenic | 0.7021 | pathogenic | -1.592 | Destabilizing | 0.864 | D | 0.611 | neutral | None | None | None | None | N |
| I/Y | 0.4091 | ambiguous | 0.3991 | ambiguous | -1.378 | Destabilizing | 0.356 | N | 0.583 | 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.