Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23185 | 69778;69779;69780 | chr2:178576691;178576690;178576689 | chr2:179441418;179441417;179441416 |
| N2AB | 21544 | 64855;64856;64857 | chr2:178576691;178576690;178576689 | chr2:179441418;179441417;179441416 |
| N2A | 20617 | 62074;62075;62076 | chr2:178576691;178576690;178576689 | chr2:179441418;179441417;179441416 |
| N2B | 14120 | 42583;42584;42585 | chr2:178576691;178576690;178576689 | chr2:179441418;179441417;179441416 |
| Novex-1 | 14245 | 42958;42959;42960 | chr2:178576691;178576690;178576689 | chr2:179441418;179441417;179441416 |
| Novex-2 | 14312 | 43159;43160;43161 | chr2:178576691;178576690;178576689 | chr2:179441418;179441417;179441416 |
| 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/Q | rs201448988  |
0.012 | 1.0 | N | 0.697 | 0.332 | None | gnomAD-2.1.1 | 5.63E-05 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 2.28773E-04 | None | 0 | 5.33E-05 | 0 |
| R/Q | rs201448988 |
0.012 | 1.0 | N | 0.697 | 0.332 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 2.07297E-04 | 0 |
| R/Q | rs201448988 |
0.012 | 1.0 | N | 0.697 | 0.332 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| R/Q | rs201448988 |
0.012 | 1.0 | N | 0.697 | 0.332 | None | gnomAD-4.0.0 | 7.80904E-05 | None | None | None | None | I | None | 4.00021E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.64694E-05 | 1.86674E-04 | 6.4041E-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 | 0.7756 | likely_pathogenic | 0.85 | pathogenic | 0.049 | Stabilizing | 0.999 | D | 0.628 | neutral | None | None | None | None | I |
| R/C | 0.3377 | likely_benign | 0.4447 | ambiguous | -0.233 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | I |
| R/D | 0.9369 | likely_pathogenic | 0.9594 | pathogenic | -0.257 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| R/E | 0.8158 | likely_pathogenic | 0.8728 | pathogenic | -0.211 | Destabilizing | 0.999 | D | 0.675 | neutral | None | None | None | None | I |
| R/F | 0.7938 | likely_pathogenic | 0.8467 | pathogenic | -0.248 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| R/G | 0.5925 | likely_pathogenic | 0.6973 | pathogenic | -0.103 | Destabilizing | 1.0 | D | 0.604 | neutral | N | 0.501874554 | None | None | I |
| R/H | 0.1669 | likely_benign | 0.2091 | benign | -0.584 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| R/I | 0.6262 | likely_pathogenic | 0.7031 | pathogenic | 0.405 | Stabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| R/K | 0.2263 | likely_benign | 0.2501 | benign | -0.14 | Destabilizing | 0.998 | D | 0.629 | neutral | None | None | None | None | I |
| R/L | 0.4959 | ambiguous | 0.5847 | pathogenic | 0.405 | Stabilizing | 1.0 | D | 0.604 | neutral | N | 0.520865746 | None | None | I |
| R/M | 0.6606 | likely_pathogenic | 0.7354 | pathogenic | -0.049 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | I |
| R/N | 0.8574 | likely_pathogenic | 0.9012 | pathogenic | -0.044 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | I |
| R/P | 0.8925 | likely_pathogenic | 0.9261 | pathogenic | 0.305 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.494486242 | None | None | I |
| R/Q | 0.218 | likely_benign | 0.2734 | benign | -0.087 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | N | 0.516574647 | None | None | I |
| R/S | 0.8363 | likely_pathogenic | 0.8915 | pathogenic | -0.249 | Destabilizing | 1.0 | D | 0.638 | neutral | None | None | None | None | I |
| R/T | 0.6792 | likely_pathogenic | 0.7777 | pathogenic | -0.09 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | I |
| R/V | 0.7013 | likely_pathogenic | 0.7744 | pathogenic | 0.305 | Stabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| R/W | 0.3254 | likely_benign | 0.3905 | ambiguous | -0.411 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | I |
| R/Y | 0.5928 | likely_pathogenic | 0.6611 | pathogenic | None | Stabilizing | 1.0 | D | 0.712 | 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.