Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35616 | 107071;107072;107073 | chr2:178528905;178528904;178528903 | chr2:179393632;179393631;179393630 |
| N2AB | 33975 | 102148;102149;102150 | chr2:178528905;178528904;178528903 | chr2:179393632;179393631;179393630 |
| N2A | 33048 | 99367;99368;99369 | chr2:178528905;178528904;178528903 | chr2:179393632;179393631;179393630 |
| N2B | 26551 | 79876;79877;79878 | chr2:178528905;178528904;178528903 | chr2:179393632;179393631;179393630 |
| Novex-1 | 26676 | 80251;80252;80253 | chr2:178528905;178528904;178528903 | chr2:179393632;179393631;179393630 |
| Novex-2 | 26743 | 80452;80453;80454 | chr2:178528905;178528904;178528903 | chr2:179393632;179393631;179393630 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/R | None | None | 0.975 | N | 0.34 | 0.45 | 0.680782376918 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| M/T | None | None | 0.425 | N | 0.297 | 0.324 | 0.668779650676 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| M/V | None | None | 0.002 | N | 0.08 | 0.208 | 0.435043484731 | gnomAD-4.0.0 | 1.36828E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31868E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5434 | ambiguous | 0.5368 | ambiguous | -1.729 | Destabilizing | 0.329 | N | 0.292 | neutral | None | None | None | None | N |
| M/C | 0.9057 | likely_pathogenic | 0.8977 | pathogenic | -1.452 | Destabilizing | 0.981 | D | 0.263 | neutral | None | None | None | None | N |
| M/D | 0.8937 | likely_pathogenic | 0.8795 | pathogenic | -0.199 | Destabilizing | 0.981 | D | 0.389 | neutral | None | None | None | None | N |
| M/E | 0.623 | likely_pathogenic | 0.6121 | pathogenic | -0.131 | Destabilizing | 0.828 | D | 0.393 | neutral | None | None | None | None | N |
| M/F | 0.3566 | ambiguous | 0.355 | ambiguous | -0.657 | Destabilizing | 0.704 | D | 0.283 | neutral | None | None | None | None | N |
| M/G | 0.7625 | likely_pathogenic | 0.7507 | pathogenic | -2.081 | Highly Destabilizing | 0.828 | D | 0.384 | neutral | None | None | None | None | N |
| M/H | 0.6508 | likely_pathogenic | 0.6388 | pathogenic | -1.06 | Destabilizing | 0.995 | D | 0.28 | neutral | None | None | None | None | N |
| M/I | 0.3779 | ambiguous | 0.3784 | ambiguous | -0.802 | Destabilizing | 0.139 | N | 0.225 | neutral | N | 0.476971401 | None | None | N |
| M/K | 0.275 | likely_benign | 0.264 | benign | -0.457 | Destabilizing | 0.784 | D | 0.319 | neutral | N | 0.479051701 | None | None | N |
| M/L | 0.1537 | likely_benign | 0.1507 | benign | -0.802 | Destabilizing | 0.001 | N | 0.079 | neutral | N | 0.457865565 | None | None | N |
| M/N | 0.6479 | likely_pathogenic | 0.6416 | pathogenic | -0.444 | Destabilizing | 0.981 | D | 0.353 | neutral | None | None | None | None | N |
| M/P | 0.9118 | likely_pathogenic | 0.8869 | pathogenic | -1.084 | Destabilizing | 0.981 | D | 0.37 | neutral | None | None | None | None | N |
| M/Q | 0.3516 | ambiguous | 0.3476 | ambiguous | -0.422 | Destabilizing | 0.981 | D | 0.265 | neutral | None | None | None | None | N |
| M/R | 0.3101 | likely_benign | 0.3045 | benign | -0.089 | Destabilizing | 0.975 | D | 0.34 | neutral | N | 0.479225059 | None | None | N |
| M/S | 0.609 | likely_pathogenic | 0.5989 | pathogenic | -1.138 | Destabilizing | 0.828 | D | 0.295 | neutral | None | None | None | None | N |
| M/T | 0.3734 | ambiguous | 0.3635 | ambiguous | -0.934 | Destabilizing | 0.425 | N | 0.297 | neutral | N | 0.478358268 | None | None | N |
| M/V | 0.1451 | likely_benign | 0.1425 | benign | -1.084 | Destabilizing | 0.002 | N | 0.08 | neutral | N | 0.473330876 | None | None | N |
| M/W | 0.738 | likely_pathogenic | 0.7268 | pathogenic | -0.586 | Destabilizing | 0.995 | D | 0.266 | neutral | None | None | None | None | N |
| M/Y | 0.6278 | likely_pathogenic | 0.6274 | pathogenic | -0.604 | Destabilizing | 0.981 | D | 0.32 | 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.