Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26605 | 80038;80039;80040 | chr2:178566319;178566318;178566317 | chr2:179431046;179431045;179431044 |
| N2AB | 24964 | 75115;75116;75117 | chr2:178566319;178566318;178566317 | chr2:179431046;179431045;179431044 |
| N2A | 24037 | 72334;72335;72336 | chr2:178566319;178566318;178566317 | chr2:179431046;179431045;179431044 |
| N2B | 17540 | 52843;52844;52845 | chr2:178566319;178566318;178566317 | chr2:179431046;179431045;179431044 |
| Novex-1 | 17665 | 53218;53219;53220 | chr2:178566319;178566318;178566317 | chr2:179431046;179431045;179431044 |
| Novex-2 | 17732 | 53419;53420;53421 | chr2:178566319;178566318;178566317 | chr2:179431046;179431045;179431044 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | None | None | 0.014 | N | 0.343 | 0.088 | 0.329282125956 | gnomAD-4.0.0 | 6.84266E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65684E-05 |
| R/T | rs1263615793  |
-0.224 | 0.822 | N | 0.567 | 0.389 | 0.517104213562 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| R/T | rs1263615793 |
-0.224 | 0.822 | N | 0.567 | 0.389 | 0.517104213562 | gnomAD-4.0.0 | 1.36853E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79904E-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 | 0.883 | likely_pathogenic | 0.8668 | pathogenic | -0.024 | Destabilizing | 0.754 | D | 0.596 | neutral | None | None | None | None | N |
| R/C | 0.4595 | ambiguous | 0.4352 | ambiguous | -0.288 | Destabilizing | 0.998 | D | 0.647 | neutral | None | None | None | None | N |
| R/D | 0.9703 | likely_pathogenic | 0.9679 | pathogenic | -0.183 | Destabilizing | 0.956 | D | 0.567 | neutral | None | None | None | None | N |
| R/E | 0.8495 | likely_pathogenic | 0.8305 | pathogenic | -0.121 | Destabilizing | 0.754 | D | 0.577 | neutral | None | None | None | None | N |
| R/F | 0.8628 | likely_pathogenic | 0.8436 | pathogenic | -0.268 | Destabilizing | 0.978 | D | 0.615 | neutral | None | None | None | None | N |
| R/G | 0.845 | likely_pathogenic | 0.8155 | pathogenic | -0.206 | Destabilizing | 0.822 | D | 0.608 | neutral | D | 0.527941681 | None | None | N |
| R/H | 0.2268 | likely_benign | 0.2211 | benign | -0.668 | Destabilizing | 0.043 | N | 0.361 | neutral | None | None | None | None | N |
| R/I | 0.746 | likely_pathogenic | 0.6865 | pathogenic | 0.419 | Stabilizing | 0.97 | D | 0.611 | neutral | N | 0.507622153 | None | None | N |
| R/K | 0.1911 | likely_benign | 0.1797 | benign | -0.18 | Destabilizing | 0.014 | N | 0.343 | neutral | N | 0.479454346 | None | None | N |
| R/L | 0.6006 | likely_pathogenic | 0.5803 | pathogenic | 0.419 | Stabilizing | 0.86 | D | 0.593 | neutral | None | None | None | None | N |
| R/M | 0.6811 | likely_pathogenic | 0.6362 | pathogenic | -0.045 | Destabilizing | 0.998 | D | 0.565 | neutral | None | None | None | None | N |
| R/N | 0.9323 | likely_pathogenic | 0.9296 | pathogenic | -0.061 | Destabilizing | 0.86 | D | 0.562 | neutral | None | None | None | None | N |
| R/P | 0.8779 | likely_pathogenic | 0.8652 | pathogenic | 0.291 | Stabilizing | 0.978 | D | 0.609 | neutral | None | None | None | None | N |
| R/Q | 0.2698 | likely_benign | 0.2543 | benign | -0.119 | Destabilizing | 0.956 | D | 0.553 | neutral | None | None | None | None | N |
| R/S | 0.9323 | likely_pathogenic | 0.9225 | pathogenic | -0.355 | Destabilizing | 0.822 | D | 0.609 | neutral | N | 0.512783032 | None | None | N |
| R/T | 0.8014 | likely_pathogenic | 0.773 | pathogenic | -0.163 | Destabilizing | 0.822 | D | 0.567 | neutral | N | 0.4949984 | None | None | N |
| R/V | 0.7851 | likely_pathogenic | 0.7535 | pathogenic | 0.291 | Stabilizing | 0.956 | D | 0.61 | neutral | None | None | None | None | N |
| R/W | 0.4429 | ambiguous | 0.3805 | ambiguous | -0.361 | Destabilizing | 0.998 | D | 0.651 | neutral | None | None | None | None | N |
| R/Y | 0.7348 | likely_pathogenic | 0.723 | pathogenic | 0.049 | Stabilizing | 0.956 | D | 0.61 | 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.