Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16497 | 49714;49715;49716 | chr2:178613794;178613793;178613792 | chr2:179478521;179478520;179478519 |
| N2AB | 14856 | 44791;44792;44793 | chr2:178613794;178613793;178613792 | chr2:179478521;179478520;179478519 |
| N2A | 13929 | 42010;42011;42012 | chr2:178613794;178613793;178613792 | chr2:179478521;179478520;179478519 |
| N2B | 7432 | 22519;22520;22521 | chr2:178613794;178613793;178613792 | chr2:179478521;179478520;179478519 |
| Novex-1 | 7557 | 22894;22895;22896 | chr2:178613794;178613793;178613792 | chr2:179478521;179478520;179478519 |
| Novex-2 | 7624 | 23095;23096;23097 | chr2:178613794;178613793;178613792 | chr2:179478521;179478520;179478519 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/R | rs748070345  |
-0.755 | 1.0 | D | 0.755 | 0.663 | 0.832326648212 | 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 |
| W/R | rs748070345 |
-0.755 | 1.0 | D | 0.755 | 0.663 | 0.832326648212 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| W/R | rs748070345 |
-0.755 | 1.0 | D | 0.755 | 0.663 | 0.832326648212 | gnomAD-4.0.0 | 2.03059E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.41026E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/A | 0.9886 | likely_pathogenic | 0.992 | pathogenic | -2.824 | Highly Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| W/C | 0.998 | likely_pathogenic | 0.9987 | pathogenic | -1.184 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | D | 0.655579577 | None | None | N |
| W/D | 0.9971 | likely_pathogenic | 0.998 | pathogenic | -1.665 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| W/E | 0.998 | likely_pathogenic | 0.9986 | pathogenic | -1.595 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| W/F | 0.7048 | likely_pathogenic | 0.697 | pathogenic | -1.704 | Destabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | N |
| W/G | 0.9807 | likely_pathogenic | 0.9866 | pathogenic | -3.018 | Highly Destabilizing | 1.0 | D | 0.677 | prob.neutral | D | 0.713724333 | None | None | N |
| W/H | 0.994 | likely_pathogenic | 0.9942 | pathogenic | -1.338 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| W/I | 0.9823 | likely_pathogenic | 0.989 | pathogenic | -2.124 | Highly Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| W/K | 0.9995 | likely_pathogenic | 0.9997 | pathogenic | -1.532 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| W/L | 0.9578 | likely_pathogenic | 0.9685 | pathogenic | -2.124 | Highly Destabilizing | 1.0 | D | 0.677 | prob.neutral | D | 0.682265203 | None | None | N |
| W/M | 0.9877 | likely_pathogenic | 0.9918 | pathogenic | -1.549 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| W/N | 0.9969 | likely_pathogenic | 0.9978 | pathogenic | -1.912 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| W/P | 0.9909 | likely_pathogenic | 0.9926 | pathogenic | -2.373 | Highly Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| W/Q | 0.9994 | likely_pathogenic | 0.9996 | pathogenic | -1.915 | Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| W/R | 0.9993 | likely_pathogenic | 0.9994 | pathogenic | -0.944 | Destabilizing | 1.0 | D | 0.755 | deleterious | D | 0.685838531 | None | None | N |
| W/S | 0.9894 | likely_pathogenic | 0.9932 | pathogenic | -2.311 | Highly Destabilizing | 1.0 | D | 0.757 | deleterious | D | 0.684626621 | None | None | N |
| W/T | 0.9898 | likely_pathogenic | 0.9932 | pathogenic | -2.198 | Highly Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| W/V | 0.9836 | likely_pathogenic | 0.9883 | pathogenic | -2.373 | Highly Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| W/Y | 0.8745 | likely_pathogenic | 0.8702 | pathogenic | -1.536 | Destabilizing | 1.0 | D | 0.601 | neutral | 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.