Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15311 | 46156;46157;46158 | chr2:178620590;178620589;178620588 | chr2:179485317;179485316;179485315 |
| N2AB | 13670 | 41233;41234;41235 | chr2:178620590;178620589;178620588 | chr2:179485317;179485316;179485315 |
| N2A | 12743 | 38452;38453;38454 | chr2:178620590;178620589;178620588 | chr2:179485317;179485316;179485315 |
| N2B | 6246 | 18961;18962;18963 | chr2:178620590;178620589;178620588 | chr2:179485317;179485316;179485315 |
| Novex-1 | 6371 | 19336;19337;19338 | chr2:178620590;178620589;178620588 | chr2:179485317;179485316;179485315 |
| Novex-2 | 6438 | 19537;19538;19539 | chr2:178620590;178620589;178620588 | chr2:179485317;179485316;179485315 |
| 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/S | None | None | 0.994 | D | 0.549 | 0.439 | 0.786388363908 | gnomAD-4.0.0 | 6.85409E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00481E-07 | 0 | 0 |
| I/T | rs769964778  |
-2.253 | 0.961 | N | 0.523 | 0.312 | 0.682452046549 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.69E-05 | 0 | 0 |
| I/T | rs769964778 |
-2.253 | 0.961 | N | 0.523 | 0.312 | 0.682452046549 | gnomAD-4.0.0 | 6.85409E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87751E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2794 | likely_benign | 0.2538 | benign | -1.68 | Destabilizing | 0.931 | D | 0.507 | neutral | None | None | None | None | N |
| I/C | 0.6255 | likely_pathogenic | 0.6538 | pathogenic | -0.98 | Destabilizing | 1.0 | D | 0.539 | neutral | None | None | None | None | N |
| I/D | 0.7404 | likely_pathogenic | 0.7043 | pathogenic | -0.986 | Destabilizing | 0.996 | D | 0.643 | neutral | None | None | None | None | N |
| I/E | 0.4592 | ambiguous | 0.4508 | ambiguous | -0.94 | Destabilizing | 0.991 | D | 0.585 | neutral | None | None | None | None | N |
| I/F | 0.2558 | likely_benign | 0.2179 | benign | -1.078 | Destabilizing | 0.994 | D | 0.519 | neutral | D | 0.559519851 | None | None | N |
| I/G | 0.7254 | likely_pathogenic | 0.6723 | pathogenic | -2.05 | Highly Destabilizing | 0.996 | D | 0.585 | neutral | None | None | None | None | N |
| I/H | 0.6082 | likely_pathogenic | 0.5588 | ambiguous | -1.283 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | N |
| I/K | 0.3633 | ambiguous | 0.3172 | benign | -1.113 | Destabilizing | 0.983 | D | 0.583 | neutral | None | None | None | None | N |
| I/L | 0.1596 | likely_benign | 0.1618 | benign | -0.717 | Destabilizing | 0.689 | D | 0.384 | neutral | N | 0.508195265 | None | None | N |
| I/M | 0.1008 | likely_benign | 0.1 | benign | -0.603 | Destabilizing | 0.994 | D | 0.521 | neutral | N | 0.512649251 | None | None | N |
| I/N | 0.345 | ambiguous | 0.3184 | benign | -0.961 | Destabilizing | 0.994 | D | 0.649 | neutral | D | 0.60400772 | None | None | N |
| I/P | 0.9598 | likely_pathogenic | 0.9366 | pathogenic | -1.007 | Destabilizing | 0.999 | D | 0.66 | neutral | None | None | None | None | N |
| I/Q | 0.4044 | ambiguous | 0.3821 | ambiguous | -1.054 | Destabilizing | 0.991 | D | 0.664 | neutral | None | None | None | None | N |
| I/R | 0.303 | likely_benign | 0.2354 | benign | -0.636 | Destabilizing | 0.191 | N | 0.437 | neutral | None | None | None | None | N |
| I/S | 0.3127 | likely_benign | 0.2722 | benign | -1.616 | Destabilizing | 0.994 | D | 0.549 | neutral | D | 0.559359102 | None | None | N |
| I/T | 0.1344 | likely_benign | 0.1031 | benign | -1.44 | Destabilizing | 0.961 | D | 0.523 | neutral | N | 0.509749634 | None | None | N |
| I/V | 0.0849 | likely_benign | 0.0736 | benign | -1.007 | Destabilizing | 0.122 | N | 0.139 | neutral | N | 0.467776504 | None | None | N |
| I/W | 0.8419 | likely_pathogenic | 0.7734 | pathogenic | -1.191 | Destabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | N |
| I/Y | 0.5764 | likely_pathogenic | 0.5719 | pathogenic | -0.949 | Destabilizing | 0.999 | D | 0.583 | 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.