Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32027 | 96304;96305;96306 | chr2:178544065;178544064;178544063 | chr2:179408792;179408791;179408790 |
| N2AB | 30386 | 91381;91382;91383 | chr2:178544065;178544064;178544063 | chr2:179408792;179408791;179408790 |
| N2A | 29459 | 88600;88601;88602 | chr2:178544065;178544064;178544063 | chr2:179408792;179408791;179408790 |
| N2B | 22962 | 69109;69110;69111 | chr2:178544065;178544064;178544063 | chr2:179408792;179408791;179408790 |
| Novex-1 | 23087 | 69484;69485;69486 | chr2:178544065;178544064;178544063 | chr2:179408792;179408791;179408790 |
| Novex-2 | 23154 | 69685;69686;69687 | chr2:178544065;178544064;178544063 | chr2:179408792;179408791;179408790 |
| 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/G | rs770295329  |
-0.421 | 1.0 | N | 0.655 | 0.52 | 0.784331960839 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/G | rs770295329 |
-0.421 | 1.0 | N | 0.655 | 0.52 | 0.784331960839 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/G | rs770295329 |
-0.421 | 1.0 | N | 0.655 | 0.52 | 0.784331960839 | gnomAD-4.0.0 | 2.02987E-06 | None | None | None | None | I | None | 1.74721E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.6966E-05 | 0 |
| R/K | None | None | 0.997 | N | 0.569 | 0.405 | 0.374434639691 | gnomAD-4.0.0 | 6.84346E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.51965E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/M | rs748483895 |
-0.292 | 1.0 | N | 0.683 | 0.551 | 0.679741279585 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| R/M | rs748483895 |
-0.292 | 1.0 | N | 0.683 | 0.551 | 0.679741279585 | gnomAD-4.0.0 | 1.36869E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31938E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9197 | likely_pathogenic | 0.9278 | pathogenic | 0.039 | Stabilizing | 0.999 | D | 0.658 | neutral | None | None | None | None | I |
| R/C | 0.5794 | likely_pathogenic | 0.5848 | pathogenic | -0.293 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | I |
| R/D | 0.9781 | likely_pathogenic | 0.9816 | pathogenic | -0.142 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| R/E | 0.881 | likely_pathogenic | 0.8963 | pathogenic | -0.068 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | I |
| R/F | 0.9234 | likely_pathogenic | 0.9307 | pathogenic | -0.22 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| R/G | 0.8815 | likely_pathogenic | 0.8859 | pathogenic | -0.142 | Destabilizing | 1.0 | D | 0.655 | neutral | N | 0.514445782 | None | None | I |
| R/H | 0.2779 | likely_benign | 0.3015 | benign | -0.71 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| R/I | 0.8552 | likely_pathogenic | 0.873 | pathogenic | 0.478 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| R/K | 0.2567 | likely_benign | 0.2706 | benign | -0.063 | Destabilizing | 0.997 | D | 0.569 | neutral | N | 0.448478078 | None | None | I |
| R/L | 0.7424 | likely_pathogenic | 0.7513 | pathogenic | 0.478 | Stabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| R/M | 0.8206 | likely_pathogenic | 0.8256 | pathogenic | -0.102 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.500963109 | None | None | I |
| R/N | 0.9585 | likely_pathogenic | 0.9648 | pathogenic | -0.058 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | I |
| R/P | 0.8808 | likely_pathogenic | 0.8809 | pathogenic | 0.352 | Stabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | I |
| R/Q | 0.3326 | likely_benign | 0.3518 | ambiguous | -0.054 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | I |
| R/S | 0.9538 | likely_pathogenic | 0.9588 | pathogenic | -0.304 | Destabilizing | 1.0 | D | 0.669 | neutral | N | 0.483487056 | None | None | I |
| R/T | 0.8748 | likely_pathogenic | 0.8869 | pathogenic | -0.095 | Destabilizing | 1.0 | D | 0.668 | neutral | D | 0.528171012 | None | None | I |
| R/V | 0.8801 | likely_pathogenic | 0.8964 | pathogenic | 0.352 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| R/W | 0.5585 | ambiguous | 0.5532 | ambiguous | -0.368 | Destabilizing | 1.0 | D | 0.763 | deleterious | D | 0.5336529 | None | None | I |
| R/Y | 0.8204 | likely_pathogenic | 0.8335 | pathogenic | 0.058 | Stabilizing | 1.0 | D | 0.725 | 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.