Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17720 | 53383;53384;53385 | chr2:178607530;178607529;178607528 | chr2:179472257;179472256;179472255 |
| N2AB | 16079 | 48460;48461;48462 | chr2:178607530;178607529;178607528 | chr2:179472257;179472256;179472255 |
| N2A | 15152 | 45679;45680;45681 | chr2:178607530;178607529;178607528 | chr2:179472257;179472256;179472255 |
| N2B | 8655 | 26188;26189;26190 | chr2:178607530;178607529;178607528 | chr2:179472257;179472256;179472255 |
| Novex-1 | 8780 | 26563;26564;26565 | chr2:178607530;178607529;178607528 | chr2:179472257;179472256;179472255 |
| Novex-2 | 8847 | 26764;26765;26766 | chr2:178607530;178607529;178607528 | chr2:179472257;179472256;179472255 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 0.997 | N | 0.555 | 0.348 | 0.690939769679 | gnomAD-4.0.0 | 1.59221E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86049E-06 | 0 | 0 |
| I/T | rs201358641  |
-1.821 | 0.978 | N | 0.57 | 0.454 | None | gnomAD-2.1.1 | 2.85914E-04 | None | None | None | None | N | None | 0 | 5.65E-05 | None | 0 | 5.13E-05 | None | 0 | None | 4.39683E-04 | 4.85521E-04 | 5.61482E-04 |
| I/T | rs201358641 |
-1.821 | 0.978 | N | 0.57 | 0.454 | None | gnomAD-3.1.2 | 2.82988E-04 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 3.7679E-04 | 0 | 5.74087E-04 | 0 | 0 |
| I/T | rs201358641 |
-1.821 | 0.978 | N | 0.57 | 0.454 | None | gnomAD-4.0.0 | 1.84118E-04 | None | None | None | None | N | None | 0 | 3.33556E-05 | None | 0 | 4.46209E-05 | None | 4.37432E-04 | 0 | 2.16211E-04 | 0 | 1.60195E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3826 | ambiguous | 0.4407 | ambiguous | -1.749 | Destabilizing | 0.983 | D | 0.451 | neutral | None | None | None | None | N |
| I/C | 0.8067 | likely_pathogenic | 0.8502 | pathogenic | -1.009 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| I/D | 0.9034 | likely_pathogenic | 0.9261 | pathogenic | -1.253 | Destabilizing | 0.999 | D | 0.736 | prob.delet. | None | None | None | None | N |
| I/E | 0.7049 | likely_pathogenic | 0.7294 | pathogenic | -1.198 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| I/F | 0.261 | likely_benign | 0.2814 | benign | -1.147 | Destabilizing | 0.998 | D | 0.534 | neutral | None | None | None | None | N |
| I/G | 0.8447 | likely_pathogenic | 0.888 | pathogenic | -2.116 | Highly Destabilizing | 0.999 | D | 0.723 | prob.delet. | None | None | None | None | N |
| I/H | 0.7913 | likely_pathogenic | 0.8266 | pathogenic | -1.259 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| I/K | 0.6144 | likely_pathogenic | 0.6615 | pathogenic | -1.21 | Destabilizing | 0.999 | D | 0.732 | prob.delet. | N | 0.514222426 | None | None | N |
| I/L | 0.1792 | likely_benign | 0.2155 | benign | -0.787 | Destabilizing | 0.798 | D | 0.364 | neutral | D | 0.526613574 | None | None | N |
| I/M | 0.113 | likely_benign | 0.1266 | benign | -0.637 | Destabilizing | 0.997 | D | 0.555 | neutral | N | 0.490291593 | None | None | N |
| I/N | 0.6179 | likely_pathogenic | 0.6813 | pathogenic | -1.131 | Destabilizing | 0.999 | D | 0.751 | deleterious | None | None | None | None | N |
| I/P | 0.8786 | likely_pathogenic | 0.9102 | pathogenic | -1.078 | Destabilizing | 0.999 | D | 0.747 | deleterious | None | None | None | None | N |
| I/Q | 0.6264 | likely_pathogenic | 0.6791 | pathogenic | -1.227 | Destabilizing | 0.999 | D | 0.749 | deleterious | None | None | None | None | N |
| I/R | 0.5166 | ambiguous | 0.5729 | pathogenic | -0.668 | Destabilizing | 0.999 | D | 0.752 | deleterious | D | 0.532415587 | None | None | N |
| I/S | 0.4846 | ambiguous | 0.5403 | ambiguous | -1.752 | Destabilizing | 0.998 | D | 0.659 | neutral | None | None | None | None | N |
| I/T | 0.1598 | likely_benign | 0.1648 | benign | -1.567 | Destabilizing | 0.978 | D | 0.57 | neutral | N | 0.508435528 | None | None | N |
| I/V | 0.106 | likely_benign | 0.0992 | benign | -1.078 | Destabilizing | 0.198 | N | 0.206 | neutral | N | 0.491439421 | None | None | N |
| I/W | 0.8279 | likely_pathogenic | 0.8515 | pathogenic | -1.266 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| I/Y | 0.7384 | likely_pathogenic | 0.7882 | pathogenic | -1.025 | Destabilizing | 0.999 | D | 0.632 | 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.