Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15975 | 48148;48149;48150 | chr2:178616966;178616965;178616964 | chr2:179481693;179481692;179481691 |
| N2AB | 14334 | 43225;43226;43227 | chr2:178616966;178616965;178616964 | chr2:179481693;179481692;179481691 |
| N2A | 13407 | 40444;40445;40446 | chr2:178616966;178616965;178616964 | chr2:179481693;179481692;179481691 |
| N2B | 6910 | 20953;20954;20955 | chr2:178616966;178616965;178616964 | chr2:179481693;179481692;179481691 |
| Novex-1 | 7035 | 21328;21329;21330 | chr2:178616966;178616965;178616964 | chr2:179481693;179481692;179481691 |
| Novex-2 | 7102 | 21529;21530;21531 | chr2:178616966;178616965;178616964 | chr2:179481693;179481692;179481691 |
| 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/T | rs755834931  |
-1.71 | 0.324 | N | 0.345 | 0.178 | 0.515938915144 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs755834931 |
-1.71 | 0.324 | N | 0.345 | 0.178 | 0.515938915144 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs755834931 |
-1.71 | 0.324 | N | 0.345 | 0.178 | 0.515938915144 | gnomAD-4.0.0 | 2.48048E-06 | None | None | None | None | N | None | 0 | 3.33767E-05 | None | 0 | 0 | None | 0 | 0 | 1.6962E-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 | 0.4852 | ambiguous | 0.4598 | ambiguous | -1.122 | Destabilizing | 0.241 | N | 0.353 | neutral | None | None | None | None | N |
| I/C | 0.7922 | likely_pathogenic | 0.7809 | pathogenic | -0.72 | Destabilizing | 0.944 | D | 0.403 | neutral | None | None | None | None | N |
| I/D | 0.8846 | likely_pathogenic | 0.8199 | pathogenic | -0.748 | Destabilizing | 0.932 | D | 0.523 | neutral | None | None | None | None | N |
| I/E | 0.7377 | likely_pathogenic | 0.6776 | pathogenic | -0.794 | Destabilizing | 0.818 | D | 0.509 | neutral | None | None | None | None | N |
| I/F | 0.2721 | likely_benign | 0.2347 | benign | -0.837 | Destabilizing | 0.001 | N | 0.207 | neutral | N | 0.433772424 | None | None | N |
| I/G | 0.887 | likely_pathogenic | 0.855 | pathogenic | -1.363 | Destabilizing | 0.818 | D | 0.473 | neutral | None | None | None | None | N |
| I/H | 0.7093 | likely_pathogenic | 0.653 | pathogenic | -0.539 | Destabilizing | 0.944 | D | 0.503 | neutral | None | None | None | None | N |
| I/K | 0.5909 | likely_pathogenic | 0.5427 | ambiguous | -0.846 | Destabilizing | 0.818 | D | 0.509 | neutral | None | None | None | None | N |
| I/L | 0.1979 | likely_benign | 0.1934 | benign | -0.571 | Destabilizing | 0.041 | N | 0.247 | neutral | N | 0.519114078 | None | None | N |
| I/M | 0.1551 | likely_benign | 0.1427 | benign | -0.504 | Destabilizing | 0.627 | D | 0.444 | neutral | D | 0.526571933 | None | None | N |
| I/N | 0.5698 | likely_pathogenic | 0.4565 | ambiguous | -0.664 | Destabilizing | 0.912 | D | 0.514 | neutral | N | 0.434043958 | None | None | N |
| I/P | 0.8088 | likely_pathogenic | 0.7812 | pathogenic | -0.722 | Destabilizing | 0.932 | D | 0.51 | neutral | None | None | None | None | N |
| I/Q | 0.6401 | likely_pathogenic | 0.5836 | pathogenic | -0.873 | Destabilizing | 0.932 | D | 0.514 | neutral | None | None | None | None | N |
| I/R | 0.4542 | ambiguous | 0.4139 | ambiguous | -0.198 | Destabilizing | 0.818 | D | 0.508 | neutral | None | None | None | None | N |
| I/S | 0.5604 | ambiguous | 0.4836 | ambiguous | -1.139 | Destabilizing | 0.627 | D | 0.457 | neutral | D | 0.523792207 | None | None | N |
| I/T | 0.2673 | likely_benign | 0.2446 | benign | -1.078 | Destabilizing | 0.324 | N | 0.345 | neutral | N | 0.482388015 | None | None | N |
| I/V | 0.104 | likely_benign | 0.1078 | benign | -0.722 | Destabilizing | 0.001 | N | 0.143 | neutral | N | 0.445695991 | None | None | N |
| I/W | 0.8494 | likely_pathogenic | 0.8168 | pathogenic | -0.885 | Destabilizing | 0.981 | D | 0.515 | neutral | None | None | None | None | N |
| I/Y | 0.6999 | likely_pathogenic | 0.6133 | pathogenic | -0.671 | Destabilizing | 0.008 | N | 0.234 | 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.