Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19233 | 57922;57923;57924 | chr2:178595657;178595656;178595655 | chr2:179460384;179460383;179460382 |
| N2AB | 17592 | 52999;53000;53001 | chr2:178595657;178595656;178595655 | chr2:179460384;179460383;179460382 |
| N2A | 16665 | 50218;50219;50220 | chr2:178595657;178595656;178595655 | chr2:179460384;179460383;179460382 |
| N2B | 10168 | 30727;30728;30729 | chr2:178595657;178595656;178595655 | chr2:179460384;179460383;179460382 |
| Novex-1 | 10293 | 31102;31103;31104 | chr2:178595657;178595656;178595655 | chr2:179460384;179460383;179460382 |
| Novex-2 | 10360 | 31303;31304;31305 | chr2:178595657;178595656;178595655 | chr2:179460384;179460383;179460382 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 0.997 | N | 0.679 | 0.389 | 0.705890645922 | gnomAD-4.0.0 | 1.60567E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.46007E-05 | 0 |
| P/S | rs766143106  |
-0.902 | 0.418 | N | 0.332 | 0.222 | 0.224531998449 | gnomAD-2.1.1 | 4.17E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.23E-06 | 0 |
| P/S | rs766143106 |
-0.902 | 0.418 | N | 0.332 | 0.222 | 0.224531998449 | gnomAD-4.0.0 | 1.6055E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87907E-06 | 0 | 0 |
| P/T | rs766143106 |
None | 0.956 | N | 0.548 | 0.304 | 0.428516003163 | gnomAD-4.0.0 | 1.6055E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.80568E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0752 | likely_benign | 0.0873 | benign | -1.061 | Destabilizing | 0.9 | D | 0.501 | neutral | N | 0.436844427 | None | None | N |
| P/C | 0.5867 | likely_pathogenic | 0.6407 | pathogenic | -0.608 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| P/D | 0.7695 | likely_pathogenic | 0.8066 | pathogenic | -0.803 | Destabilizing | 0.983 | D | 0.615 | neutral | None | None | None | None | N |
| P/E | 0.5486 | ambiguous | 0.6048 | pathogenic | -0.851 | Destabilizing | 0.983 | D | 0.618 | neutral | None | None | None | None | N |
| P/F | 0.7792 | likely_pathogenic | 0.8161 | pathogenic | -0.943 | Destabilizing | 0.999 | D | 0.751 | deleterious | None | None | None | None | N |
| P/G | 0.4226 | ambiguous | 0.4262 | ambiguous | -1.309 | Destabilizing | 0.983 | D | 0.573 | neutral | None | None | None | None | N |
| P/H | 0.385 | ambiguous | 0.4356 | ambiguous | -0.811 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| P/I | 0.5372 | ambiguous | 0.5933 | pathogenic | -0.513 | Destabilizing | 0.998 | D | 0.767 | deleterious | None | None | None | None | N |
| P/K | 0.5849 | likely_pathogenic | 0.654 | pathogenic | -0.851 | Destabilizing | 0.983 | D | 0.616 | neutral | None | None | None | None | N |
| P/L | 0.2253 | likely_benign | 0.2683 | benign | -0.513 | Destabilizing | 0.997 | D | 0.679 | prob.neutral | N | 0.42559007 | None | None | N |
| P/M | 0.4623 | ambiguous | 0.4993 | ambiguous | -0.381 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| P/N | 0.5106 | ambiguous | 0.5366 | ambiguous | -0.561 | Destabilizing | 0.995 | D | 0.667 | neutral | None | None | None | None | N |
| P/Q | 0.2879 | likely_benign | 0.3147 | benign | -0.772 | Destabilizing | 0.997 | D | 0.722 | prob.delet. | N | 0.440538093 | None | None | N |
| P/R | 0.3928 | ambiguous | 0.4599 | ambiguous | -0.293 | Destabilizing | 0.997 | D | 0.751 | deleterious | N | 0.410369902 | None | None | N |
| P/S | 0.1503 | likely_benign | 0.1668 | benign | -1.0 | Destabilizing | 0.418 | N | 0.332 | neutral | N | 0.403481215 | None | None | N |
| P/T | 0.1404 | likely_benign | 0.1703 | benign | -0.943 | Destabilizing | 0.956 | D | 0.548 | neutral | N | 0.401961062 | None | None | N |
| P/V | 0.3145 | likely_benign | 0.3614 | ambiguous | -0.66 | Destabilizing | 0.998 | D | 0.663 | neutral | None | None | None | None | N |
| P/W | 0.8765 | likely_pathogenic | 0.8951 | pathogenic | -1.084 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | N |
| P/Y | 0.7324 | likely_pathogenic | 0.7722 | pathogenic | -0.795 | Destabilizing | 0.999 | D | 0.753 | deleterious | 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.