Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24849 | 74770;74771;74772 | chr2:178571587;178571586;178571585 | chr2:179436314;179436313;179436312 |
| N2AB | 23208 | 69847;69848;69849 | chr2:178571587;178571586;178571585 | chr2:179436314;179436313;179436312 |
| N2A | 22281 | 67066;67067;67068 | chr2:178571587;178571586;178571585 | chr2:179436314;179436313;179436312 |
| N2B | 15784 | 47575;47576;47577 | chr2:178571587;178571586;178571585 | chr2:179436314;179436313;179436312 |
| Novex-1 | 15909 | 47950;47951;47952 | chr2:178571587;178571586;178571585 | chr2:179436314;179436313;179436312 |
| Novex-2 | 15976 | 48151;48152;48153 | chr2:178571587;178571586;178571585 | chr2:179436314;179436313;179436312 |
| 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/L | None | None | 0.954 | N | 0.606 | 0.501 | 0.516050471323 | gnomAD-4.0.0 | 6.84466E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53062E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs745488276  |
-1.306 | 0.59 | N | 0.317 | 0.362 | 0.229924730088 | gnomAD-2.1.1 | 2.83E-05 | None | None | None | None | N | None | 0 | 1.16239E-04 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.8E-05 | 0 |
| R/Q | rs745488276 |
-1.306 | 0.59 | N | 0.317 | 0.362 | 0.229924730088 | gnomAD-4.0.0 | 9.5825E-06 | None | None | None | None | N | None | 0 | 8.94815E-05 | None | 0 | 0 | None | 0 | 0 | 7.19694E-06 | 1.15964E-05 | 1.65772E-05 |
| R/W | rs727503562 |
-1.061 | 1.0 | N | 0.671 | 0.571 | 0.369495900351 | gnomAD-2.1.1 | 2.51E-05 | None | None | None | None | N | None | 2.07159E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.58E-05 | 0 |
| R/W | rs727503562 |
-1.061 | 1.0 | N | 0.671 | 0.571 | 0.369495900351 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 1.44872E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/W | rs727503562 |
-1.061 | 1.0 | N | 0.671 | 0.571 | 0.369495900351 | gnomAD-4.0.0 | 9.29914E-06 | None | None | None | None | N | None | 1.20221E-04 | 0 | None | 0 | 0 | None | 0 | 1.64636E-04 | 3.39105E-06 | 1.09808E-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 | 0.981 | likely_pathogenic | 0.9802 | pathogenic | -1.997 | Destabilizing | 0.916 | D | 0.519 | neutral | None | None | None | None | N |
| R/C | 0.6345 | likely_pathogenic | 0.6042 | pathogenic | -2.044 | Highly Destabilizing | 0.999 | D | 0.714 | prob.delet. | None | None | None | None | N |
| R/D | 0.9985 | likely_pathogenic | 0.9984 | pathogenic | -1.005 | Destabilizing | 0.975 | D | 0.647 | neutral | None | None | None | None | N |
| R/E | 0.9755 | likely_pathogenic | 0.9736 | pathogenic | -0.828 | Destabilizing | 0.845 | D | 0.449 | neutral | None | None | None | None | N |
| R/F | 0.9893 | likely_pathogenic | 0.9866 | pathogenic | -1.613 | Destabilizing | 0.996 | D | 0.753 | deleterious | None | None | None | None | N |
| R/G | 0.9723 | likely_pathogenic | 0.9686 | pathogenic | -2.315 | Highly Destabilizing | 0.954 | D | 0.606 | neutral | N | 0.512594178 | None | None | N |
| R/H | 0.7441 | likely_pathogenic | 0.6967 | pathogenic | -2.212 | Highly Destabilizing | 0.987 | D | 0.553 | neutral | None | None | None | None | N |
| R/I | 0.9702 | likely_pathogenic | 0.9688 | pathogenic | -1.09 | Destabilizing | 0.987 | D | 0.759 | deleterious | None | None | None | None | N |
| R/K | 0.4968 | ambiguous | 0.4602 | ambiguous | -1.588 | Destabilizing | 0.693 | D | 0.439 | neutral | None | None | None | None | N |
| R/L | 0.9419 | likely_pathogenic | 0.9317 | pathogenic | -1.09 | Destabilizing | 0.954 | D | 0.606 | neutral | N | 0.491754445 | None | None | N |
| R/M | 0.9375 | likely_pathogenic | 0.929 | pathogenic | -1.395 | Destabilizing | 0.997 | D | 0.669 | neutral | None | None | None | None | N |
| R/N | 0.9927 | likely_pathogenic | 0.9923 | pathogenic | -1.353 | Destabilizing | 0.975 | D | 0.523 | neutral | None | None | None | None | N |
| R/P | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -1.379 | Destabilizing | 0.993 | D | 0.717 | prob.delet. | N | 0.521241459 | None | None | N |
| R/Q | 0.5676 | likely_pathogenic | 0.5275 | ambiguous | -1.414 | Destabilizing | 0.59 | D | 0.317 | neutral | N | 0.478610487 | None | None | N |
| R/S | 0.9929 | likely_pathogenic | 0.9928 | pathogenic | -2.307 | Highly Destabilizing | 0.916 | D | 0.575 | neutral | None | None | None | None | N |
| R/T | 0.9844 | likely_pathogenic | 0.9841 | pathogenic | -1.927 | Destabilizing | 0.975 | D | 0.646 | neutral | None | None | None | None | N |
| R/V | 0.9733 | likely_pathogenic | 0.9725 | pathogenic | -1.379 | Destabilizing | 0.975 | D | 0.745 | deleterious | None | None | None | None | N |
| R/W | 0.9001 | likely_pathogenic | 0.8792 | pathogenic | -1.118 | Destabilizing | 1.0 | D | 0.671 | neutral | N | 0.493475965 | None | None | N |
| R/Y | 0.9578 | likely_pathogenic | 0.9487 | pathogenic | -0.908 | Destabilizing | 0.996 | D | 0.735 | 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.