Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14808 | 44647;44648;44649 | chr2:178629303;178629302;178629301 | chr2:179494030;179494029;179494028 |
| N2AB | 13167 | 39724;39725;39726 | chr2:178629303;178629302;178629301 | chr2:179494030;179494029;179494028 |
| N2A | 12240 | 36943;36944;36945 | chr2:178629303;178629302;178629301 | chr2:179494030;179494029;179494028 |
| N2B | 5743 | 17452;17453;17454 | chr2:178629303;178629302;178629301 | chr2:179494030;179494029;179494028 |
| Novex-1 | 5868 | 17827;17828;17829 | chr2:178629303;178629302;178629301 | chr2:179494030;179494029;179494028 |
| Novex-2 | 5935 | 18028;18029;18030 | chr2:178629303;178629302;178629301 | chr2:179494030;179494029;179494028 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | None | None | 0.09 | N | 0.263 | 0.194 | 0.18995819373 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| K/N | rs762657962  |
0.043 | 0.324 | N | 0.297 | 0.105 | 0.117506650769 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| K/N | rs762657962 |
0.043 | 0.324 | N | 0.297 | 0.105 | 0.117506650769 | gnomAD-4.0.0 | 1.59544E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86466E-06 | 0 | 0 |
| K/T | rs374419129 |
-0.31 | 0.001 | N | 0.191 | 0.126 | None | gnomAD-2.1.1 | 4.3E-05 | None | None | None | None | N | None | 1.6559E-04 | 1.99022E-04 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| K/T | rs374419129 |
-0.31 | 0.001 | N | 0.191 | 0.126 | None | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 2.17181E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.79386E-04 |
| K/T | rs374419129 |
-0.31 | 0.001 | N | 0.191 | 0.126 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 8E-04 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| K/T | rs374419129 |
-0.31 | 0.001 | N | 0.191 | 0.126 | None | gnomAD-4.0.0 | 4.89972E-05 | None | None | None | None | N | None | 6.26934E-04 | 1.16787E-04 | None | 0 | 0 | None | 0 | 3.30688E-04 | 5.08886E-06 | 1.09982E-05 | 2.56451E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.249 | likely_benign | 0.2866 | benign | -0.285 | Destabilizing | 0.116 | N | 0.249 | neutral | None | None | None | None | N |
| K/C | 0.6956 | likely_pathogenic | 0.696 | pathogenic | -0.274 | Destabilizing | 0.944 | D | 0.395 | neutral | None | None | None | None | N |
| K/D | 0.4151 | ambiguous | 0.4598 | ambiguous | 0.128 | Stabilizing | 0.388 | N | 0.351 | neutral | None | None | None | None | N |
| K/E | 0.1632 | likely_benign | 0.2136 | benign | 0.207 | Stabilizing | 0.09 | N | 0.263 | neutral | N | 0.518962267 | None | None | N |
| K/F | 0.6847 | likely_pathogenic | 0.7112 | pathogenic | -0.121 | Destabilizing | 0.818 | D | 0.387 | neutral | None | None | None | None | N |
| K/G | 0.3986 | ambiguous | 0.4449 | ambiguous | -0.617 | Destabilizing | 0.388 | N | 0.313 | neutral | None | None | None | None | N |
| K/H | 0.239 | likely_benign | 0.2489 | benign | -1.036 | Destabilizing | 0.818 | D | 0.311 | neutral | None | None | None | None | N |
| K/I | 0.2741 | likely_benign | 0.3038 | benign | 0.551 | Stabilizing | 0.527 | D | 0.405 | neutral | None | None | None | None | N |
| K/L | 0.287 | likely_benign | 0.3096 | benign | 0.551 | Stabilizing | 0.241 | N | 0.307 | neutral | None | None | None | None | N |
| K/M | 0.1988 | likely_benign | 0.2292 | benign | 0.427 | Stabilizing | 0.773 | D | 0.309 | neutral | D | 0.546890963 | None | None | N |
| K/N | 0.2719 | likely_benign | 0.3145 | benign | -0.101 | Destabilizing | 0.324 | N | 0.297 | neutral | N | 0.454008018 | None | None | N |
| K/P | 0.7651 | likely_pathogenic | 0.7828 | pathogenic | 0.304 | Stabilizing | 0.818 | D | 0.351 | neutral | None | None | None | None | N |
| K/Q | 0.1229 | likely_benign | 0.1398 | benign | -0.193 | Destabilizing | 0.006 | N | 0.177 | neutral | N | 0.445830495 | None | None | N |
| K/R | 0.0817 | likely_benign | 0.082 | benign | -0.428 | Destabilizing | 0.001 | N | 0.112 | neutral | N | 0.411910428 | None | None | N |
| K/S | 0.312 | likely_benign | 0.3467 | ambiguous | -0.715 | Destabilizing | 0.241 | N | 0.223 | neutral | None | None | None | None | N |
| K/T | 0.1135 | likely_benign | 0.1235 | benign | -0.44 | Destabilizing | 0.001 | N | 0.191 | neutral | N | 0.448364815 | None | None | N |
| K/V | 0.2709 | likely_benign | 0.2967 | benign | 0.304 | Stabilizing | 0.241 | N | 0.367 | neutral | None | None | None | None | N |
| K/W | 0.7092 | likely_pathogenic | 0.7267 | pathogenic | -0.042 | Destabilizing | 0.981 | D | 0.443 | neutral | None | None | None | None | N |
| K/Y | 0.5119 | ambiguous | 0.5338 | ambiguous | 0.27 | Stabilizing | 0.818 | D | 0.348 | 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.