Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1296 | 4111;4112;4113 | chr2:178779306;178779305;178779304 | chr2:179644033;179644032;179644031 |
| N2AB | 1296 | 4111;4112;4113 | chr2:178779306;178779305;178779304 | chr2:179644033;179644032;179644031 |
| N2A | 1296 | 4111;4112;4113 | chr2:178779306;178779305;178779304 | chr2:179644033;179644032;179644031 |
| N2B | 1250 | 3973;3974;3975 | chr2:178779306;178779305;178779304 | chr2:179644033;179644032;179644031 |
| Novex-1 | 1250 | 3973;3974;3975 | chr2:178779306;178779305;178779304 | chr2:179644033;179644032;179644031 |
| Novex-2 | 1250 | 3973;3974;3975 | chr2:178779306;178779305;178779304 | chr2:179644033;179644032;179644031 |
| Novex-3 | 1296 | 4111;4112;4113 | chr2:178779306;178779305;178779304 | chr2:179644033;179644032;179644031 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs754853658  |
-0.444 | 0.959 | N | 0.575 | 0.417 | 0.498641525541 | gnomAD-2.1.1 | 4E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| R/G | rs754853658 |
-0.444 | 0.959 | N | 0.575 | 0.417 | 0.498641525541 | gnomAD-4.0.0 | 6.84262E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15966E-05 | 0 |
| R/K | rs2092554276 |
None | 0.061 | N | 0.222 | 0.214 | 0.219573609325 | gnomAD-4.0.0 | 3.6017E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.93835E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5558 | ambiguous | 0.5775 | pathogenic | -0.401 | Destabilizing | 0.863 | D | 0.502 | neutral | None | None | None | None | N |
| R/C | 0.361 | ambiguous | 0.3623 | ambiguous | -0.496 | Destabilizing | 0.999 | D | 0.566 | neutral | None | None | None | None | N |
| R/D | 0.8273 | likely_pathogenic | 0.8301 | pathogenic | 0.109 | Stabilizing | 0.969 | D | 0.587 | neutral | None | None | None | None | N |
| R/E | 0.5803 | likely_pathogenic | 0.5637 | ambiguous | 0.209 | Stabilizing | 0.939 | D | 0.513 | neutral | None | None | None | None | N |
| R/F | 0.7905 | likely_pathogenic | 0.7922 | pathogenic | -0.501 | Destabilizing | 0.997 | D | 0.565 | neutral | None | None | None | None | N |
| R/G | 0.4353 | ambiguous | 0.4566 | ambiguous | -0.642 | Destabilizing | 0.959 | D | 0.575 | neutral | N | 0.503651326 | None | None | N |
| R/H | 0.182 | likely_benign | 0.1842 | benign | -1.105 | Destabilizing | 0.997 | D | 0.589 | neutral | None | None | None | None | N |
| R/I | 0.5535 | ambiguous | 0.5342 | ambiguous | 0.215 | Stabilizing | 0.996 | D | 0.58 | neutral | N | 0.508289739 | None | None | N |
| R/K | 0.1503 | likely_benign | 0.1532 | benign | -0.297 | Destabilizing | 0.061 | N | 0.222 | neutral | N | 0.445151473 | None | None | N |
| R/L | 0.4445 | ambiguous | 0.4466 | ambiguous | 0.215 | Stabilizing | 0.969 | D | 0.577 | neutral | None | None | None | None | N |
| R/M | 0.5632 | ambiguous | 0.5633 | ambiguous | -0.219 | Destabilizing | 0.997 | D | 0.567 | neutral | None | None | None | None | N |
| R/N | 0.7618 | likely_pathogenic | 0.7785 | pathogenic | -0.029 | Destabilizing | 0.969 | D | 0.552 | neutral | None | None | None | None | N |
| R/P | 0.4621 | ambiguous | 0.4437 | ambiguous | 0.031 | Stabilizing | 0.02 | N | 0.323 | neutral | None | None | None | None | N |
| R/Q | 0.167 | likely_benign | 0.1677 | benign | -0.133 | Destabilizing | 0.939 | D | 0.555 | neutral | None | None | None | None | N |
| R/S | 0.6878 | likely_pathogenic | 0.7069 | pathogenic | -0.616 | Destabilizing | 0.92 | D | 0.539 | neutral | N | 0.501710381 | None | None | N |
| R/T | 0.4904 | ambiguous | 0.4987 | ambiguous | -0.35 | Destabilizing | 0.959 | D | 0.54 | neutral | N | 0.499687427 | None | None | N |
| R/V | 0.5628 | ambiguous | 0.5607 | ambiguous | 0.031 | Stabilizing | 0.969 | D | 0.586 | neutral | None | None | None | None | N |
| R/W | 0.4442 | ambiguous | 0.4292 | ambiguous | -0.396 | Destabilizing | 0.999 | D | 0.595 | neutral | None | None | None | None | N |
| R/Y | 0.6639 | likely_pathogenic | 0.6575 | pathogenic | -0.025 | Destabilizing | 0.997 | D | 0.583 | 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.