Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30916 | 92971;92972;92973 | chr2:178548880;178548879;178548878 | chr2:179413607;179413606;179413605 |
| N2AB | 29275 | 88048;88049;88050 | chr2:178548880;178548879;178548878 | chr2:179413607;179413606;179413605 |
| N2A | 28348 | 85267;85268;85269 | chr2:178548880;178548879;178548878 | chr2:179413607;179413606;179413605 |
| N2B | 21851 | 65776;65777;65778 | chr2:178548880;178548879;178548878 | chr2:179413607;179413606;179413605 |
| Novex-1 | 21976 | 66151;66152;66153 | chr2:178548880;178548879;178548878 | chr2:179413607;179413606;179413605 |
| Novex-2 | 22043 | 66352;66353;66354 | chr2:178548880;178548879;178548878 | chr2:179413607;179413606;179413605 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/E | None | None | 0.986 | N | 0.759 | 0.481 | 0.727266359203 | gnomAD-4.0.0 | 6.84241E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65662E-05 |
| A/V | rs770400064  |
-0.542 | 0.908 | N | 0.556 | 0.32 | 0.48300943003 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| A/V | rs770400064 |
-0.542 | 0.908 | N | 0.556 | 0.32 | 0.48300943003 | gnomAD-4.0.0 | 6.84241E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99437E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6498 | likely_pathogenic | 0.6368 | pathogenic | -1.383 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| A/D | 0.975 | likely_pathogenic | 0.9713 | pathogenic | -1.724 | Destabilizing | 0.989 | D | 0.819 | deleterious | None | None | None | None | N |
| A/E | 0.9476 | likely_pathogenic | 0.9455 | pathogenic | -1.773 | Destabilizing | 0.986 | D | 0.759 | deleterious | N | 0.519267947 | None | None | N |
| A/F | 0.9247 | likely_pathogenic | 0.9218 | pathogenic | -1.229 | Destabilizing | 0.995 | D | 0.823 | deleterious | None | None | None | None | N |
| A/G | 0.429 | ambiguous | 0.3926 | ambiguous | -1.046 | Destabilizing | 0.952 | D | 0.566 | neutral | N | 0.508761015 | None | None | N |
| A/H | 0.982 | likely_pathogenic | 0.9808 | pathogenic | -1.063 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| A/I | 0.4319 | ambiguous | 0.4183 | ambiguous | -0.476 | Destabilizing | 0.989 | D | 0.775 | deleterious | None | None | None | None | N |
| A/K | 0.9833 | likely_pathogenic | 0.9832 | pathogenic | -1.057 | Destabilizing | 0.989 | D | 0.761 | deleterious | None | None | None | None | N |
| A/L | 0.4197 | ambiguous | 0.4072 | ambiguous | -0.476 | Destabilizing | 0.929 | D | 0.701 | prob.delet. | None | None | None | None | N |
| A/M | 0.4639 | ambiguous | 0.4542 | ambiguous | -0.519 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| A/N | 0.8769 | likely_pathogenic | 0.8625 | pathogenic | -0.966 | Destabilizing | 0.989 | D | 0.821 | deleterious | None | None | None | None | N |
| A/P | 0.2704 | likely_benign | 0.2587 | benign | -0.565 | Destabilizing | 0.993 | D | 0.803 | deleterious | N | 0.521626255 | None | None | N |
| A/Q | 0.9398 | likely_pathogenic | 0.9374 | pathogenic | -1.234 | Destabilizing | 0.995 | D | 0.793 | deleterious | None | None | None | None | N |
| A/R | 0.9659 | likely_pathogenic | 0.9686 | pathogenic | -0.681 | Destabilizing | 0.989 | D | 0.807 | deleterious | None | None | None | None | N |
| A/S | 0.2877 | likely_benign | 0.2657 | benign | -1.258 | Destabilizing | 0.908 | D | 0.553 | neutral | N | 0.518760968 | None | None | N |
| A/T | 0.1953 | likely_benign | 0.1668 | benign | -1.224 | Destabilizing | 0.208 | N | 0.308 | neutral | N | 0.484527468 | None | None | N |
| A/V | 0.1805 | likely_benign | 0.162 | benign | -0.565 | Destabilizing | 0.908 | D | 0.556 | neutral | N | 0.456809559 | None | None | N |
| A/W | 0.9917 | likely_pathogenic | 0.992 | pathogenic | -1.468 | Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| A/Y | 0.9706 | likely_pathogenic | 0.97 | pathogenic | -1.055 | Destabilizing | 0.998 | D | 0.821 | 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.