Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24083 | 72472;72473;72474 | chr2:178573885;178573884;178573883 | chr2:179438612;179438611;179438610 |
| N2AB | 22442 | 67549;67550;67551 | chr2:178573885;178573884;178573883 | chr2:179438612;179438611;179438610 |
| N2A | 21515 | 64768;64769;64770 | chr2:178573885;178573884;178573883 | chr2:179438612;179438611;179438610 |
| N2B | 15018 | 45277;45278;45279 | chr2:178573885;178573884;178573883 | chr2:179438612;179438611;179438610 |
| Novex-1 | 15143 | 45652;45653;45654 | chr2:178573885;178573884;178573883 | chr2:179438612;179438611;179438610 |
| Novex-2 | 15210 | 45853;45854;45855 | chr2:178573885;178573884;178573883 | chr2:179438612;179438611;179438610 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | None | None | 0.989 | N | 0.593 | 0.418 | 0.463243292966 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 1.94099E-04 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| F/V | rs759548192  |
-0.235 | 0.989 | N | 0.639 | 0.45 | 0.705680399256 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.56E-05 | None | 0 | 0 | 1.66611E-04 |
| F/V | rs759548192 |
-0.235 | 0.989 | N | 0.639 | 0.45 | 0.705680399256 | gnomAD-4.0.0 | 4.79262E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86952E-05 | 3.0349E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.5124 | ambiguous | 0.4517 | ambiguous | -1.567 | Destabilizing | 0.996 | D | 0.591 | neutral | None | None | None | None | N |
| F/C | 0.3575 | ambiguous | 0.319 | benign | -0.491 | Destabilizing | 1.0 | D | 0.651 | neutral | N | 0.500758845 | None | None | N |
| F/D | 0.6151 | likely_pathogenic | 0.5359 | ambiguous | 0.26 | Stabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| F/E | 0.7874 | likely_pathogenic | 0.7264 | pathogenic | 0.266 | Stabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| F/G | 0.6518 | likely_pathogenic | 0.5678 | pathogenic | -1.824 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| F/H | 0.5455 | ambiguous | 0.4597 | ambiguous | -0.307 | Destabilizing | 0.999 | D | 0.637 | neutral | None | None | None | None | N |
| F/I | 0.2148 | likely_benign | 0.2037 | benign | -0.859 | Destabilizing | 0.998 | D | 0.637 | neutral | N | 0.50573687 | None | None | N |
| F/K | 0.7909 | likely_pathogenic | 0.7203 | pathogenic | -0.426 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | None | None | None | None | N |
| F/L | 0.8207 | likely_pathogenic | 0.8125 | pathogenic | -0.859 | Destabilizing | 0.989 | D | 0.593 | neutral | N | 0.488324545 | None | None | N |
| F/M | 0.5089 | ambiguous | 0.4593 | ambiguous | -0.552 | Destabilizing | 1.0 | D | 0.63 | neutral | None | None | None | None | N |
| F/N | 0.4491 | ambiguous | 0.3771 | ambiguous | -0.265 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| F/P | 0.9748 | likely_pathogenic | 0.9627 | pathogenic | -1.08 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| F/Q | 0.7417 | likely_pathogenic | 0.6723 | pathogenic | -0.394 | Destabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | N |
| F/R | 0.6759 | likely_pathogenic | 0.6112 | pathogenic | 0.175 | Stabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| F/S | 0.328 | likely_benign | 0.292 | benign | -1.054 | Destabilizing | 0.998 | D | 0.659 | neutral | N | 0.447168569 | None | None | N |
| F/T | 0.4003 | ambiguous | 0.3494 | ambiguous | -0.956 | Destabilizing | 0.999 | D | 0.662 | neutral | None | None | None | None | N |
| F/V | 0.2297 | likely_benign | 0.2178 | benign | -1.08 | Destabilizing | 0.989 | D | 0.639 | neutral | N | 0.509969254 | None | None | N |
| F/W | 0.6156 | likely_pathogenic | 0.5407 | ambiguous | -0.476 | Destabilizing | 1.0 | D | 0.627 | neutral | None | None | None | None | N |
| F/Y | 0.1503 | likely_benign | 0.1271 | benign | -0.511 | Destabilizing | 0.543 | D | 0.294 | neutral | N | 0.464351607 | 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.