Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30592 | 91999;92000;92001 | chr2:178550064;178550063;178550062 | chr2:179414791;179414790;179414789 |
| N2AB | 28951 | 87076;87077;87078 | chr2:178550064;178550063;178550062 | chr2:179414791;179414790;179414789 |
| N2A | 28024 | 84295;84296;84297 | chr2:178550064;178550063;178550062 | chr2:179414791;179414790;179414789 |
| N2B | 21527 | 64804;64805;64806 | chr2:178550064;178550063;178550062 | chr2:179414791;179414790;179414789 |
| Novex-1 | 21652 | 65179;65180;65181 | chr2:178550064;178550063;178550062 | chr2:179414791;179414790;179414789 |
| Novex-2 | 21719 | 65380;65381;65382 | chr2:178550064;178550063;178550062 | chr2:179414791;179414790;179414789 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | None | None | 0.22 | N | 0.439 | 0.192 | 0.110078149338 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| D/N | rs767435344  |
0.539 | 0.002 | N | 0.197 | 0.193 | 0.0846915920261 | gnomAD-2.1.1 | 1.16561E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.47836E-04 | None | 0 | 0 | 0 |
| D/N | rs767435344 |
0.539 | 0.002 | N | 0.197 | 0.193 | 0.0846915920261 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 6.22148E-04 | 0 |
| D/N | rs767435344 |
0.539 | 0.002 | N | 0.197 | 0.193 | 0.0846915920261 | gnomAD-4.0.0 | 5.08154E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47621E-07 | 8.56465E-04 | 4.80323E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1587 | likely_benign | 0.1801 | benign | -0.313 | Destabilizing | 0.124 | N | 0.469 | neutral | N | 0.388060684 | None | None | I |
| D/C | 0.5457 | ambiguous | 0.5674 | pathogenic | -0.105 | Destabilizing | 0.968 | D | 0.609 | neutral | None | None | None | None | I |
| D/E | 0.1005 | likely_benign | 0.1055 | benign | -0.245 | Destabilizing | None | N | 0.195 | neutral | N | 0.379457057 | None | None | I |
| D/F | 0.4736 | ambiguous | 0.5086 | ambiguous | -0.209 | Destabilizing | 0.89 | D | 0.561 | neutral | None | None | None | None | I |
| D/G | 0.1818 | likely_benign | 0.1989 | benign | -0.523 | Destabilizing | 0.22 | N | 0.439 | neutral | N | 0.426386999 | None | None | I |
| D/H | 0.2698 | likely_benign | 0.2918 | benign | -0.053 | Destabilizing | 0.667 | D | 0.463 | neutral | N | 0.465945465 | None | None | I |
| D/I | 0.2918 | likely_benign | 0.3236 | benign | 0.198 | Stabilizing | 0.726 | D | 0.556 | neutral | None | None | None | None | I |
| D/K | 0.3623 | ambiguous | 0.385 | ambiguous | 0.016 | Stabilizing | 0.157 | N | 0.443 | neutral | None | None | None | None | I |
| D/L | 0.2934 | likely_benign | 0.3227 | benign | 0.198 | Stabilizing | 0.567 | D | 0.516 | neutral | None | None | None | None | I |
| D/M | 0.4565 | ambiguous | 0.4946 | ambiguous | 0.288 | Stabilizing | 0.968 | D | 0.555 | neutral | None | None | None | None | I |
| D/N | 0.1065 | likely_benign | 0.1236 | benign | -0.152 | Destabilizing | 0.002 | N | 0.197 | neutral | N | 0.391831708 | None | None | I |
| D/P | 0.7904 | likely_pathogenic | 0.8157 | pathogenic | 0.05 | Stabilizing | 0.726 | D | 0.465 | neutral | None | None | None | None | I |
| D/Q | 0.2583 | likely_benign | 0.276 | benign | -0.113 | Destabilizing | 0.396 | N | 0.415 | neutral | None | None | None | None | I |
| D/R | 0.4052 | ambiguous | 0.4286 | ambiguous | 0.267 | Stabilizing | 0.396 | N | 0.472 | neutral | None | None | None | None | I |
| D/S | 0.1261 | likely_benign | 0.139 | benign | -0.33 | Destabilizing | 0.157 | N | 0.423 | neutral | None | None | None | None | I |
| D/T | 0.2229 | likely_benign | 0.2469 | benign | -0.174 | Destabilizing | 0.272 | N | 0.483 | neutral | None | None | None | None | I |
| D/V | 0.1918 | likely_benign | 0.2149 | benign | 0.05 | Stabilizing | 0.497 | N | 0.521 | neutral | N | 0.466118823 | None | None | I |
| D/W | 0.8134 | likely_pathogenic | 0.8304 | pathogenic | -0.09 | Destabilizing | 0.968 | D | 0.674 | neutral | None | None | None | None | I |
| D/Y | 0.204 | likely_benign | 0.2181 | benign | 0.009 | Stabilizing | 0.859 | D | 0.559 | neutral | N | 0.475815742 | None | None | I |
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.