Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9710 | 29353;29354;29355 | chr2:178706868;178706867;178706866 | chr2:179571595;179571594;179571593 |
| N2AB | 9393 | 28402;28403;28404 | chr2:178706868;178706867;178706866 | chr2:179571595;179571594;179571593 |
| N2A | 8466 | 25621;25622;25623 | chr2:178706868;178706867;178706866 | chr2:179571595;179571594;179571593 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/E | rs1196573815  |
None | 0.175 | None | 0.526 | 0.28 | 0.673560067753 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/E | rs1196573815 |
None | 0.175 | None | 0.526 | 0.28 | 0.673560067753 | gnomAD-4.0.0 | 1.31385E-05 | None | None | None | None | I | None | 4.82369E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs72649002 |
-0.278 | 0.004 | None | 0.189 | 0.084 | None | gnomAD-2.1.1 | 1.51403E-03 | None | None | None | None | I | None | 5.42979E-04 | 2.00481E-04 | None | 0 | 1.94468E-02 | None | 6.67E-05 | None | 0 | 1.11201E-04 | 1.13443E-03 |
| V/I | rs72649002 |
-0.278 | 0.004 | None | 0.189 | 0.084 | None | gnomAD-3.1.2 | 1.01852E-03 | None | None | None | None | I | None | 5.54859E-04 | 1.50583E-03 | 0 | 0 | 1.90458E-02 | None | 0 | 0 | 2.94E-05 | 4.14422E-04 | 2.86533E-03 |
| V/I | rs72649002 |
-0.278 | 0.004 | None | 0.189 | 0.084 | None | 1000 genomes | 4.59265E-03 | None | None | None | None | I | None | 0 | 1.4E-03 | None | None | 2.18E-02 | 0 | None | None | None | 0 | None |
| V/I | rs72649002 |
-0.278 | 0.004 | None | 0.189 | 0.084 | None | gnomAD-4.0.0 | 5.45984E-04 | None | None | None | None | I | None | 4.66617E-04 | 5.35475E-04 | None | 0 | 1.24649E-02 | None | 0 | 1.65071E-04 | 5.17499E-05 | 1.76526E-04 | 2.82033E-03 |
| V/L | None | None | 0.001 | None | 0.174 | 0.076 | 0.307016933798 | gnomAD-4.0.0 | 6.85181E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.0031E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2414 | likely_benign | 0.1563 | benign | -0.868 | Destabilizing | 0.081 | N | 0.223 | neutral | None | None | None | None | I |
| V/C | 0.8722 | likely_pathogenic | 0.7033 | pathogenic | -0.759 | Destabilizing | 0.958 | D | 0.433 | neutral | None | None | None | None | I |
| V/D | 0.6165 | likely_pathogenic | 0.3855 | ambiguous | -0.648 | Destabilizing | 0.364 | N | 0.501 | neutral | None | None | None | None | I |
| V/E | 0.4289 | ambiguous | 0.2981 | benign | -0.745 | Destabilizing | 0.175 | N | 0.526 | neutral | None | None | None | None | I |
| V/F | 0.2755 | likely_benign | 0.16 | benign | -0.912 | Destabilizing | 0.497 | N | 0.443 | neutral | None | None | None | None | I |
| V/G | 0.4083 | ambiguous | 0.2433 | benign | -1.05 | Destabilizing | 0.001 | N | 0.351 | neutral | None | None | None | None | I |
| V/H | 0.774 | likely_pathogenic | 0.5575 | ambiguous | -0.535 | Destabilizing | 0.958 | D | 0.487 | neutral | None | None | None | None | I |
| V/I | 0.0782 | likely_benign | 0.0802 | benign | -0.522 | Destabilizing | 0.004 | N | 0.189 | neutral | None | None | None | None | I |
| V/K | 0.493 | ambiguous | 0.3033 | benign | -0.75 | Destabilizing | 0.22 | N | 0.523 | neutral | None | None | None | None | I |
| V/L | 0.2139 | likely_benign | 0.1302 | benign | -0.522 | Destabilizing | 0.001 | N | 0.174 | neutral | None | None | None | None | I |
| V/M | 0.1375 | likely_benign | 0.0944 | benign | -0.409 | Destabilizing | 0.025 | N | 0.189 | neutral | None | None | None | None | I |
| V/N | 0.4333 | ambiguous | 0.2287 | benign | -0.499 | Destabilizing | 0.667 | D | 0.525 | neutral | None | None | None | None | I |
| V/P | 0.6216 | likely_pathogenic | 0.4076 | ambiguous | -0.601 | Destabilizing | None | N | 0.286 | neutral | None | None | None | None | I |
| V/Q | 0.4474 | ambiguous | 0.3067 | benign | -0.776 | Destabilizing | 0.667 | D | 0.519 | neutral | None | None | None | None | I |
| V/R | 0.4697 | ambiguous | 0.2492 | benign | -0.147 | Destabilizing | 0.667 | D | 0.513 | neutral | None | None | None | None | I |
| V/S | 0.3335 | likely_benign | 0.187 | benign | -0.909 | Destabilizing | 0.124 | N | 0.483 | neutral | None | None | None | None | I |
| V/T | 0.1986 | likely_benign | 0.1276 | benign | -0.908 | Destabilizing | 0.002 | N | 0.174 | neutral | None | None | None | None | I |
| V/W | 0.876 | likely_pathogenic | 0.696 | pathogenic | -0.975 | Destabilizing | 0.958 | D | 0.502 | neutral | None | None | None | None | I |
| V/Y | 0.7486 | likely_pathogenic | 0.5318 | ambiguous | -0.7 | Destabilizing | 0.667 | D | 0.437 | 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.