Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2434 | 7525;7526;7527 | chr2:178773868;178773867;178773866 | chr2:179638595;179638594;179638593 |
| N2AB | 2434 | 7525;7526;7527 | chr2:178773868;178773867;178773866 | chr2:179638595;179638594;179638593 |
| N2A | 2434 | 7525;7526;7527 | chr2:178773868;178773867;178773866 | chr2:179638595;179638594;179638593 |
| N2B | 2388 | 7387;7388;7389 | chr2:178773868;178773867;178773866 | chr2:179638595;179638594;179638593 |
| Novex-1 | 2388 | 7387;7388;7389 | chr2:178773868;178773867;178773866 | chr2:179638595;179638594;179638593 |
| Novex-2 | 2388 | 7387;7388;7389 | chr2:178773868;178773867;178773866 | chr2:179638595;179638594;179638593 |
| Novex-3 | 2434 | 7525;7526;7527 | chr2:178773868;178773867;178773866 | chr2:179638595;179638594;179638593 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/H | rs774798625  |
-1.079 | 0.999 | N | 0.783 | 0.499 | 0.843933267728 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| L/H | rs774798625 |
-1.079 | 0.999 | N | 0.783 | 0.499 | 0.843933267728 | gnomAD-4.0.0 | 3.42042E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49653E-06 | 0 | 0 |
| L/R | rs774798625 |
-0.349 | 0.984 | N | 0.739 | 0.506 | None | gnomAD-2.1.1 | 7.99E-06 | None | None | None | None | N | None | 1.23062E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/R | rs774798625 |
-0.349 | 0.984 | N | 0.739 | 0.506 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/R | rs774798625 |
-0.349 | 0.984 | N | 0.739 | 0.506 | None | gnomAD-4.0.0 | 4.33712E-06 | None | None | None | None | N | None | 9.34405E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.3504 | ambiguous | 0.3789 | ambiguous | -1.344 | Destabilizing | 0.919 | D | 0.625 | neutral | None | None | None | None | N |
| L/C | 0.5193 | ambiguous | 0.5421 | ambiguous | -1.114 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | N |
| L/D | 0.7677 | likely_pathogenic | 0.7923 | pathogenic | -0.278 | Destabilizing | 0.996 | D | 0.778 | deleterious | None | None | None | None | N |
| L/E | 0.4433 | ambiguous | 0.4703 | ambiguous | -0.256 | Destabilizing | 0.988 | D | 0.77 | deleterious | None | None | None | None | N |
| L/F | 0.1195 | likely_benign | 0.1221 | benign | -0.85 | Destabilizing | 0.968 | D | 0.627 | neutral | N | 0.479535147 | None | None | N |
| L/G | 0.668 | likely_pathogenic | 0.687 | pathogenic | -1.667 | Destabilizing | 0.988 | D | 0.768 | deleterious | None | None | None | None | N |
| L/H | 0.2472 | likely_benign | 0.2632 | benign | -0.873 | Destabilizing | 0.999 | D | 0.783 | deleterious | N | 0.481595253 | None | None | N |
| L/I | 0.082 | likely_benign | 0.0821 | benign | -0.54 | Destabilizing | 0.011 | N | 0.225 | neutral | N | 0.35254417 | None | None | N |
| L/K | 0.2995 | likely_benign | 0.3133 | benign | -0.862 | Destabilizing | 0.976 | D | 0.731 | prob.delet. | None | None | None | None | N |
| L/M | 0.1106 | likely_benign | 0.1142 | benign | -0.613 | Destabilizing | 0.702 | D | 0.405 | neutral | None | None | None | None | N |
| L/N | 0.4509 | ambiguous | 0.4827 | ambiguous | -0.78 | Destabilizing | 0.988 | D | 0.781 | deleterious | None | None | None | None | N |
| L/P | 0.8277 | likely_pathogenic | 0.8495 | pathogenic | -0.776 | Destabilizing | 0.995 | D | 0.781 | deleterious | N | 0.481595253 | None | None | N |
| L/Q | 0.1763 | likely_benign | 0.1879 | benign | -0.851 | Destabilizing | 0.988 | D | 0.74 | deleterious | None | None | None | None | N |
| L/R | 0.2608 | likely_benign | 0.2723 | benign | -0.433 | Destabilizing | 0.984 | D | 0.739 | prob.delet. | N | 0.481122547 | None | None | N |
| L/S | 0.3912 | ambiguous | 0.4186 | ambiguous | -1.472 | Destabilizing | 0.976 | D | 0.697 | prob.neutral | None | None | None | None | N |
| L/T | 0.3145 | likely_benign | 0.3403 | ambiguous | -1.315 | Destabilizing | 0.919 | D | 0.643 | neutral | None | None | None | None | N |
| L/V | 0.0976 | likely_benign | 0.1029 | benign | -0.776 | Destabilizing | 0.64 | D | 0.416 | neutral | N | 0.459594217 | None | None | N |
| L/W | 0.3191 | likely_benign | 0.3364 | benign | -0.903 | Destabilizing | 0.999 | D | 0.759 | deleterious | None | None | None | None | N |
| L/Y | 0.3242 | likely_benign | 0.3339 | benign | -0.66 | Destabilizing | 0.988 | D | 0.725 | prob.delet. | None | None | 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.