Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19409 | 58450;58451;58452 | chr2:178594168;178594167;178594166 | chr2:179458895;179458894;179458893 |
| N2AB | 17768 | 53527;53528;53529 | chr2:178594168;178594167;178594166 | chr2:179458895;179458894;179458893 |
| N2A | 16841 | 50746;50747;50748 | chr2:178594168;178594167;178594166 | chr2:179458895;179458894;179458893 |
| N2B | 10344 | 31255;31256;31257 | chr2:178594168;178594167;178594166 | chr2:179458895;179458894;179458893 |
| Novex-1 | 10469 | 31630;31631;31632 | chr2:178594168;178594167;178594166 | chr2:179458895;179458894;179458893 |
| Novex-2 | 10536 | 31831;31832;31833 | chr2:178594168;178594167;178594166 | chr2:179458895;179458894;179458893 |
| 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 | rs553606996  |
-0.286 | 0.999 | N | 0.721 | 0.405 | 0.826570024253 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs553606996 |
-0.286 | 0.999 | N | 0.721 | 0.405 | 0.826570024253 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/C | rs553606996 |
-0.286 | 0.999 | N | 0.721 | 0.405 | 0.826570024253 | gnomAD-4.0.0 | 5.57866E-06 | None | None | None | None | I | None | 0 | 3.33656E-05 | None | 3.37906E-05 | 4.47708E-05 | None | 0 | 0 | 2.54326E-06 | 1.0981E-05 | 0 |
| R/H | rs201505306 |
-1.025 | 0.069 | N | 0.385 | 0.138 | None | gnomAD-2.1.1 | 2.71978E-04 | None | None | None | None | I | None | 2.60417E-03 | 5.67E-05 | None | 0 | 5.18E-05 | None | 0 | None | 0 | 7.05E-05 | 1.40687E-04 |
| R/H | rs201505306 |
-1.025 | 0.069 | N | 0.385 | 0.138 | None | gnomAD-3.1.2 | 6.90571E-04 | None | None | None | None | I | None | 2.36498E-03 | 1.31096E-04 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 4.80307E-04 |
| R/H | rs201505306 |
-1.025 | 0.069 | N | 0.385 | 0.138 | None | gnomAD-4.0.0 | 1.32655E-04 | None | None | None | None | I | None | 2.16288E-03 | 1.50175E-04 | None | 0 | 2.23724E-05 | None | 0 | 0 | 3.05187E-05 | 0 | 9.61076E-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 | 0.4179 | ambiguous | 0.344 | ambiguous | -0.101 | Destabilizing | 0.707 | D | 0.628 | neutral | None | None | None | None | I |
| R/C | 0.151 | likely_benign | 0.1105 | benign | -0.228 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | N | 0.488227678 | None | None | I |
| R/D | 0.6356 | likely_pathogenic | 0.5489 | ambiguous | -0.073 | Destabilizing | 0.894 | D | 0.675 | prob.neutral | None | None | None | None | I |
| R/E | 0.3625 | ambiguous | 0.3128 | benign | -0.014 | Destabilizing | 0.547 | D | 0.61 | neutral | None | None | None | None | I |
| R/F | 0.4977 | ambiguous | 0.3811 | ambiguous | -0.334 | Destabilizing | 0.894 | D | 0.731 | prob.delet. | None | None | None | None | I |
| R/G | 0.318 | likely_benign | 0.2589 | benign | -0.294 | Destabilizing | 0.822 | D | 0.651 | neutral | N | 0.495861001 | None | None | I |
| R/H | 0.0862 | likely_benign | 0.0668 | benign | -0.723 | Destabilizing | 0.069 | N | 0.385 | neutral | N | 0.519436886 | None | None | I |
| R/I | 0.23 | likely_benign | 0.2014 | benign | 0.369 | Stabilizing | 0.945 | D | 0.731 | prob.delet. | None | None | None | None | I |
| R/K | 0.1074 | likely_benign | 0.1036 | benign | -0.156 | Destabilizing | 0.499 | N | 0.535 | neutral | None | None | None | None | I |
| R/L | 0.2588 | likely_benign | 0.2095 | benign | 0.369 | Stabilizing | 0.942 | D | 0.647 | neutral | D | 0.524632062 | None | None | I |
| R/M | 0.2821 | likely_benign | 0.2639 | benign | 0.009 | Stabilizing | 0.995 | D | 0.682 | prob.neutral | None | None | None | None | I |
| R/N | 0.4523 | ambiguous | 0.3636 | ambiguous | 0.107 | Stabilizing | 0.547 | D | 0.638 | neutral | None | None | None | None | I |
| R/P | 0.8915 | likely_pathogenic | 0.8659 | pathogenic | 0.233 | Stabilizing | 0.97 | D | 0.729 | prob.delet. | N | 0.445979277 | None | None | I |
| R/Q | 0.1044 | likely_benign | 0.0878 | benign | -0.026 | Destabilizing | 0.894 | D | 0.656 | neutral | None | None | None | None | I |
| R/S | 0.3965 | ambiguous | 0.3203 | benign | -0.297 | Destabilizing | 0.822 | D | 0.652 | neutral | N | 0.498906898 | None | None | I |
| R/T | 0.1958 | likely_benign | 0.1759 | benign | -0.105 | Destabilizing | 0.945 | D | 0.651 | neutral | None | None | None | None | I |
| R/V | 0.3098 | likely_benign | 0.265 | benign | 0.233 | Stabilizing | 0.945 | D | 0.725 | prob.delet. | None | None | None | None | I |
| R/W | 0.2064 | likely_benign | 0.1626 | benign | -0.355 | Destabilizing | 0.995 | D | 0.706 | prob.neutral | None | None | None | None | I |
| R/Y | 0.3513 | ambiguous | 0.2448 | benign | 0.048 | Stabilizing | 0.809 | D | 0.731 | prob.delet. | 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.