Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2725 | 8398;8399;8400 | chr2:178770619;178770618;178770617 | chr2:179635346;179635345;179635344 |
| N2AB | 2725 | 8398;8399;8400 | chr2:178770619;178770618;178770617 | chr2:179635346;179635345;179635344 |
| N2A | 2725 | 8398;8399;8400 | chr2:178770619;178770618;178770617 | chr2:179635346;179635345;179635344 |
| N2B | 2679 | 8260;8261;8262 | chr2:178770619;178770618;178770617 | chr2:179635346;179635345;179635344 |
| Novex-1 | 2679 | 8260;8261;8262 | chr2:178770619;178770618;178770617 | chr2:179635346;179635345;179635344 |
| Novex-2 | 2679 | 8260;8261;8262 | chr2:178770619;178770618;178770617 | chr2:179635346;179635345;179635344 |
| Novex-3 | 2725 | 8398;8399;8400 | chr2:178770619;178770618;178770617 | chr2:179635346;179635345;179635344 |
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/A | rs146979556  |
-1.359 | 0.656 | D | 0.52 | 0.524 | None | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | N | None | 6.15E-05 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs146979556 |
-1.359 | 0.656 | D | 0.52 | 0.524 | None | gnomAD-4.0.0 | 1.59074E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77362E-05 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | None | None | 0.014 | D | 0.351 | 0.184 | 0.43046518545 | gnomAD-4.0.0 | 4.80129E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.9375E-06 | 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 | 0.1617 | likely_benign | 0.1582 | benign | -1.193 | Destabilizing | 0.656 | D | 0.52 | neutral | D | 0.679360648 | None | None | N |
| V/C | 0.6617 | likely_pathogenic | 0.6705 | pathogenic | -0.912 | Destabilizing | 0.998 | D | 0.7 | prob.neutral | None | None | None | None | N |
| V/D | 0.2243 | likely_benign | 0.2295 | benign | -0.539 | Destabilizing | 0.971 | D | 0.74 | deleterious | D | 0.638976866 | None | None | N |
| V/E | 0.1754 | likely_benign | 0.1785 | benign | -0.518 | Destabilizing | 0.978 | D | 0.718 | prob.delet. | None | None | None | None | N |
| V/F | 0.154 | likely_benign | 0.1412 | benign | -0.816 | Destabilizing | 0.942 | D | 0.719 | prob.delet. | D | 0.678550291 | None | None | N |
| V/G | 0.2356 | likely_benign | 0.2326 | benign | -1.516 | Destabilizing | 0.971 | D | 0.712 | prob.delet. | D | 0.615833133 | None | None | N |
| V/H | 0.4389 | ambiguous | 0.4296 | ambiguous | -0.89 | Destabilizing | 0.998 | D | 0.733 | prob.delet. | None | None | None | None | N |
| V/I | 0.0723 | likely_benign | 0.0661 | benign | -0.412 | Destabilizing | 0.014 | N | 0.351 | neutral | D | 0.547538241 | None | None | N |
| V/K | 0.3125 | likely_benign | 0.3185 | benign | -0.887 | Destabilizing | 0.978 | D | 0.714 | prob.delet. | None | None | None | None | N |
| V/L | 0.1119 | likely_benign | 0.1081 | benign | -0.412 | Destabilizing | 0.247 | N | 0.435 | neutral | D | 0.599901931 | None | None | N |
| V/M | 0.1039 | likely_benign | 0.0951 | benign | -0.459 | Destabilizing | 0.956 | D | 0.621 | neutral | None | None | None | None | N |
| V/N | 0.1708 | likely_benign | 0.1618 | benign | -0.77 | Destabilizing | 0.978 | D | 0.759 | deleterious | None | None | None | None | N |
| V/P | 0.8623 | likely_pathogenic | 0.8715 | pathogenic | -0.636 | Destabilizing | 0.993 | D | 0.726 | prob.delet. | None | None | None | None | N |
| V/Q | 0.2584 | likely_benign | 0.2571 | benign | -0.858 | Destabilizing | 0.993 | D | 0.737 | prob.delet. | None | None | None | None | N |
| V/R | 0.2929 | likely_benign | 0.2897 | benign | -0.458 | Destabilizing | 0.978 | D | 0.763 | deleterious | None | None | None | None | N |
| V/S | 0.1514 | likely_benign | 0.1547 | benign | -1.37 | Destabilizing | 0.915 | D | 0.677 | prob.neutral | None | None | None | None | N |
| V/T | 0.1326 | likely_benign | 0.132 | benign | -1.22 | Destabilizing | 0.076 | N | 0.365 | neutral | None | None | None | None | N |
| V/W | 0.747 | likely_pathogenic | 0.73 | pathogenic | -0.972 | Destabilizing | 0.998 | D | 0.698 | prob.neutral | None | None | None | None | N |
| V/Y | 0.4253 | ambiguous | 0.4324 | ambiguous | -0.66 | Destabilizing | 0.978 | D | 0.731 | 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.