Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5364 | 16315;16316;16317 | chr2:178733086;178733085;178733084 | chr2:179597813;179597812;179597811 |
| N2AB | 5047 | 15364;15365;15366 | chr2:178733086;178733085;178733084 | chr2:179597813;179597812;179597811 |
| N2A | 4120 | 12583;12584;12585 | chr2:178733086;178733085;178733084 | chr2:179597813;179597812;179597811 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/C | rs886044310  |
None | 0.998 | N | 0.363 | 0.424 | 0.715147219533 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.93125E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs886044310 |
None | 0.998 | N | 0.363 | 0.424 | 0.715147219533 | gnomAD-4.0.0 | 2.05879E-05 | None | None | None | None | I | None | 1.34084E-05 | 1.69096E-05 | None | 0 | 2.24054E-05 | None | 0 | 0 | 2.13062E-05 | 2.23249E-05 | 4.84293E-05 |
| R/H | rs200941841 |
-0.542 | 0.98 | N | 0.475 | 0.401 | None | gnomAD-2.1.1 | 1.46628E-04 | None | None | None | None | I | None | 1.66016E-04 | 5.82E-05 | None | 5.18242E-04 | 7.75996E-04 | None | 3.47E-05 | None | 4.07E-05 | 9.59E-05 | 0 |
| R/H | rs200941841 |
-0.542 | 0.98 | N | 0.475 | 0.401 | None | gnomAD-3.1.2 | 1.24896E-04 | None | None | None | None | I | None | 9.65E-05 | 1.31027E-04 | 0 | 1.15207E-03 | 1.1583E-03 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/H | rs200941841 |
-0.542 | 0.98 | N | 0.475 | 0.401 | None | gnomAD-4.0.0 | 7.17317E-05 | None | None | None | None | I | None | 8.03105E-05 | 1.6901E-04 | None | 5.50888E-04 | 4.25837E-04 | None | 1.56927E-05 | 0 | 4.09054E-05 | 3.34769E-05 | 1.9368E-04 |
| R/L | None | None | 0.756 | N | 0.463 | 0.396 | 0.627711000292 | gnomAD-4.0.0 | 1.37841E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80927E-06 | 0 | 0 |
| R/S | None | None | 0.608 | N | 0.443 | 0.244 | 0.432716982437 | gnomAD-4.0.0 | 6.893E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.67073E-05 |
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 | 0.4322 | ambiguous | 0.4084 | ambiguous | 0.127 | Stabilizing | 0.25 | N | 0.425 | neutral | None | None | None | None | I |
| R/C | 0.2302 | likely_benign | 0.2251 | benign | -0.043 | Destabilizing | 0.998 | D | 0.363 | neutral | N | 0.51524593 | None | None | I |
| R/D | 0.6999 | likely_pathogenic | 0.6956 | pathogenic | -0.045 | Destabilizing | 0.617 | D | 0.464 | neutral | None | None | None | None | I |
| R/E | 0.4092 | ambiguous | 0.3762 | ambiguous | 0.033 | Stabilizing | 0.25 | N | 0.435 | neutral | None | None | None | None | I |
| R/F | 0.5994 | likely_pathogenic | 0.6065 | pathogenic | -0.031 | Destabilizing | 0.972 | D | 0.385 | neutral | None | None | None | None | I |
| R/G | 0.2398 | likely_benign | 0.2194 | benign | -0.086 | Destabilizing | 0.004 | N | 0.232 | neutral | N | 0.4971909 | None | None | I |
| R/H | 0.1253 | likely_benign | 0.1255 | benign | -0.641 | Destabilizing | 0.98 | D | 0.475 | neutral | N | 0.495874227 | None | None | I |
| R/I | 0.3581 | ambiguous | 0.3278 | benign | 0.654 | Stabilizing | 0.92 | D | 0.411 | neutral | None | None | None | None | I |
| R/K | 0.0984 | likely_benign | 0.0919 | benign | 0.064 | Stabilizing | 0.001 | N | 0.161 | neutral | None | None | None | None | I |
| R/L | 0.2917 | likely_benign | 0.2883 | benign | 0.654 | Stabilizing | 0.756 | D | 0.463 | neutral | N | 0.49744439 | None | None | I |
| R/M | 0.3388 | likely_benign | 0.3011 | benign | 0.108 | Stabilizing | 0.972 | D | 0.434 | neutral | None | None | None | None | I |
| R/N | 0.5861 | likely_pathogenic | 0.5771 | pathogenic | 0.251 | Stabilizing | 0.617 | D | 0.433 | neutral | None | None | None | None | I |
| R/P | 0.6095 | likely_pathogenic | 0.6014 | pathogenic | 0.5 | Stabilizing | 0.957 | D | 0.411 | neutral | N | 0.494811044 | None | None | I |
| R/Q | 0.1101 | likely_benign | 0.1037 | benign | 0.197 | Stabilizing | 0.447 | N | 0.464 | neutral | None | None | None | None | I |
| R/S | 0.5065 | ambiguous | 0.484 | ambiguous | -0.047 | Destabilizing | 0.608 | D | 0.443 | neutral | N | 0.513817635 | None | None | I |
| R/T | 0.3274 | likely_benign | 0.2904 | benign | 0.173 | Stabilizing | 0.617 | D | 0.455 | neutral | None | None | None | None | I |
| R/V | 0.4147 | ambiguous | 0.3954 | ambiguous | 0.5 | Stabilizing | 0.617 | D | 0.431 | neutral | None | None | None | None | I |
| R/W | 0.1875 | likely_benign | 0.1858 | benign | -0.104 | Destabilizing | 0.992 | D | 0.387 | neutral | None | None | None | None | I |
| R/Y | 0.4224 | ambiguous | 0.4356 | ambiguous | 0.311 | Stabilizing | 0.972 | D | 0.417 | 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.