Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16491 | 49696;49697;49698 | chr2:178613812;178613811;178613810 | chr2:179478539;179478538;179478537 |
| N2AB | 14850 | 44773;44774;44775 | chr2:178613812;178613811;178613810 | chr2:179478539;179478538;179478537 |
| N2A | 13923 | 41992;41993;41994 | chr2:178613812;178613811;178613810 | chr2:179478539;179478538;179478537 |
| N2B | 7426 | 22501;22502;22503 | chr2:178613812;178613811;178613810 | chr2:179478539;179478538;179478537 |
| Novex-1 | 7551 | 22876;22877;22878 | chr2:178613812;178613811;178613810 | chr2:179478539;179478538;179478537 |
| Novex-2 | 7618 | 23077;23078;23079 | chr2:178613812;178613811;178613810 | chr2:179478539;179478538;179478537 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs1464618103  |
-1.318 | 0.989 | N | 0.531 | 0.418 | 0.326616659874 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| D/N | None | None | 0.989 | N | 0.485 | 0.294 | 0.365703291355 | gnomAD-4.0.0 | 6.84644E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16025E-05 | 0 |
| D/Y | None | None | 1.0 | D | 0.742 | 0.358 | 0.580379909603 | gnomAD-4.0.0 | 6.84644E-07 | None | None | None | None | N | None | 2.99365E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.5761 | likely_pathogenic | 0.5566 | ambiguous | -0.548 | Destabilizing | 0.978 | D | 0.546 | neutral | N | 0.471099576 | None | None | N |
| D/C | 0.7875 | likely_pathogenic | 0.7573 | pathogenic | -0.388 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | N |
| D/E | 0.3209 | likely_benign | 0.2866 | benign | -0.975 | Destabilizing | 0.198 | N | 0.133 | neutral | N | 0.428151412 | None | None | N |
| D/F | 0.8668 | likely_pathogenic | 0.8683 | pathogenic | -0.438 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| D/G | 0.8559 | likely_pathogenic | 0.8523 | pathogenic | -0.905 | Destabilizing | 0.989 | D | 0.531 | neutral | N | 0.482124864 | None | None | N |
| D/H | 0.6783 | likely_pathogenic | 0.6706 | pathogenic | -0.917 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | D | 0.549761823 | None | None | N |
| D/I | 0.6633 | likely_pathogenic | 0.5993 | pathogenic | 0.397 | Stabilizing | 0.999 | D | 0.771 | deleterious | None | None | None | None | N |
| D/K | 0.9335 | likely_pathogenic | 0.9242 | pathogenic | -0.874 | Destabilizing | 0.983 | D | 0.533 | neutral | None | None | None | None | N |
| D/L | 0.6545 | likely_pathogenic | 0.6054 | pathogenic | 0.397 | Stabilizing | 0.998 | D | 0.757 | deleterious | None | None | None | None | N |
| D/M | 0.8874 | likely_pathogenic | 0.8513 | pathogenic | 0.932 | Stabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| D/N | 0.3742 | ambiguous | 0.3363 | benign | -1.196 | Destabilizing | 0.989 | D | 0.485 | neutral | N | 0.479407089 | None | None | N |
| D/P | 0.9644 | likely_pathogenic | 0.9645 | pathogenic | 0.108 | Stabilizing | 0.999 | D | 0.734 | prob.delet. | None | None | None | None | N |
| D/Q | 0.8111 | likely_pathogenic | 0.7827 | pathogenic | -1.019 | Destabilizing | 0.995 | D | 0.581 | neutral | None | None | None | None | N |
| D/R | 0.9389 | likely_pathogenic | 0.9366 | pathogenic | -0.804 | Destabilizing | 0.995 | D | 0.738 | prob.delet. | None | None | None | None | N |
| D/S | 0.48 | ambiguous | 0.4466 | ambiguous | -1.489 | Destabilizing | 0.983 | D | 0.429 | neutral | None | None | None | None | N |
| D/T | 0.7797 | likely_pathogenic | 0.731 | pathogenic | -1.198 | Destabilizing | 0.998 | D | 0.612 | neutral | None | None | None | None | N |
| D/V | 0.5547 | ambiguous | 0.5006 | ambiguous | 0.108 | Stabilizing | 0.997 | D | 0.755 | deleterious | N | 0.464407969 | None | None | N |
| D/W | 0.9792 | likely_pathogenic | 0.9785 | pathogenic | -0.447 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/Y | 0.5446 | ambiguous | 0.5474 | ambiguous | -0.275 | Destabilizing | 1.0 | D | 0.742 | deleterious | D | 0.645247318 | 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.