Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15987 | 48184;48185;48186 | chr2:178616930;178616929;178616928 | chr2:179481657;179481656;179481655 |
| N2AB | 14346 | 43261;43262;43263 | chr2:178616930;178616929;178616928 | chr2:179481657;179481656;179481655 |
| N2A | 13419 | 40480;40481;40482 | chr2:178616930;178616929;178616928 | chr2:179481657;179481656;179481655 |
| N2B | 6922 | 20989;20990;20991 | chr2:178616930;178616929;178616928 | chr2:179481657;179481656;179481655 |
| Novex-1 | 7047 | 21364;21365;21366 | chr2:178616930;178616929;178616928 | chr2:179481657;179481656;179481655 |
| Novex-2 | 7114 | 21565;21566;21567 | chr2:178616930;178616929;178616928 | chr2:179481657;179481656;179481655 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.981 | D | 0.478 | 0.413 | 0.499921029546 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 3.66327E-05 |
| T/I | rs1429436042  |
0.114 | 0.999 | D | 0.671 | 0.502 | 0.658336924587 | gnomAD-2.1.1 | 7.17E-06 | None | None | None | None | I | None | 8.28E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs1429436042 |
0.114 | 0.999 | D | 0.671 | 0.502 | 0.658336924587 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs1429436042 |
0.114 | 0.999 | D | 0.671 | 0.502 | 0.658336924587 | gnomAD-4.0.0 | 3.10075E-06 | None | None | None | None | I | None | 6.68682E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.097 | likely_benign | 0.0994 | benign | -0.19 | Destabilizing | 0.981 | D | 0.478 | neutral | D | 0.559420239 | None | None | I |
| T/C | 0.4722 | ambiguous | 0.4748 | ambiguous | -0.332 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | I |
| T/D | 0.546 | ambiguous | 0.5558 | ambiguous | -0.03 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | I |
| T/E | 0.3982 | ambiguous | 0.401 | ambiguous | -0.126 | Destabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | I |
| T/F | 0.3197 | likely_benign | 0.349 | ambiguous | -0.885 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | I |
| T/G | 0.3327 | likely_benign | 0.3295 | benign | -0.221 | Destabilizing | 0.997 | D | 0.553 | neutral | None | None | None | None | I |
| T/H | 0.3008 | likely_benign | 0.2882 | benign | -0.425 | Destabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | I |
| T/I | 0.2366 | likely_benign | 0.2575 | benign | -0.224 | Destabilizing | 0.999 | D | 0.671 | neutral | D | 0.626216847 | None | None | I |
| T/K | 0.1819 | likely_benign | 0.1803 | benign | -0.254 | Destabilizing | 0.999 | D | 0.638 | neutral | N | 0.505384125 | None | None | I |
| T/L | 0.1614 | likely_benign | 0.172 | benign | -0.224 | Destabilizing | 0.998 | D | 0.606 | neutral | None | None | None | None | I |
| T/M | 0.1362 | likely_benign | 0.1434 | benign | -0.164 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| T/N | 0.1928 | likely_benign | 0.1942 | benign | -0.049 | Destabilizing | 0.999 | D | 0.614 | neutral | None | None | None | None | I |
| T/P | 0.4726 | ambiguous | 0.5405 | ambiguous | -0.191 | Destabilizing | 0.999 | D | 0.667 | neutral | D | 0.628973865 | None | None | I |
| T/Q | 0.253 | likely_benign | 0.2427 | benign | -0.254 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| T/R | 0.1488 | likely_benign | 0.1596 | benign | -0.022 | Destabilizing | 0.999 | D | 0.665 | neutral | N | 0.511977946 | None | None | I |
| T/S | 0.1321 | likely_benign | 0.1312 | benign | -0.203 | Destabilizing | 0.905 | D | 0.298 | neutral | N | 0.506700863 | None | None | I |
| T/V | 0.1668 | likely_benign | 0.176 | benign | -0.191 | Destabilizing | 0.998 | D | 0.555 | neutral | None | None | None | None | I |
| T/W | 0.6763 | likely_pathogenic | 0.7016 | pathogenic | -0.976 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | I |
| T/Y | 0.3502 | ambiguous | 0.3735 | ambiguous | -0.656 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | 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.