Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26097 | 78514;78515;78516 | chr2:178567843;178567842;178567841 | chr2:179432570;179432569;179432568 |
| N2AB | 24456 | 73591;73592;73593 | chr2:178567843;178567842;178567841 | chr2:179432570;179432569;179432568 |
| N2A | 23529 | 70810;70811;70812 | chr2:178567843;178567842;178567841 | chr2:179432570;179432569;179432568 |
| N2B | 17032 | 51319;51320;51321 | chr2:178567843;178567842;178567841 | chr2:179432570;179432569;179432568 |
| Novex-1 | 17157 | 51694;51695;51696 | chr2:178567843;178567842;178567841 | chr2:179432570;179432569;179432568 |
| Novex-2 | 17224 | 51895;51896;51897 | chr2:178567843;178567842;178567841 | chr2:179432570;179432569;179432568 |
| 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/Q | rs375623167  |
-0.814 | 0.484 | N | 0.657 | 0.294 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| P/R | rs375623167 |
-0.439 | 0.317 | N | 0.68 | 0.289 | 0.351180957027 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.65E-05 | 0 | 0 |
| P/R | rs375623167 |
-0.439 | 0.317 | N | 0.68 | 0.289 | 0.351180957027 | gnomAD-4.0.0 | 3.18376E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.76875E-05 | 0 | 0 | 0 | 0 |
| P/S | None | None | 0.027 | N | 0.441 | 0.088 | 0.15556083564 | gnomAD-4.0.0 | 1.36863E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79917E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0486 | likely_benign | 0.0519 | benign | -1.63 | Destabilizing | None | N | 0.333 | neutral | N | 0.332212976 | None | None | N |
| P/C | 0.495 | ambiguous | 0.5314 | ambiguous | -1.119 | Destabilizing | 0.555 | D | 0.671 | neutral | None | None | None | None | N |
| P/D | 0.8628 | likely_pathogenic | 0.8625 | pathogenic | -1.536 | Destabilizing | 0.149 | N | 0.586 | neutral | None | None | None | None | N |
| P/E | 0.7075 | likely_pathogenic | 0.7271 | pathogenic | -1.464 | Destabilizing | 0.149 | N | 0.587 | neutral | None | None | None | None | N |
| P/F | 0.7355 | likely_pathogenic | 0.7181 | pathogenic | -1.063 | Destabilizing | 0.555 | D | 0.687 | prob.neutral | None | None | None | None | N |
| P/G | 0.385 | ambiguous | 0.3874 | ambiguous | -2.029 | Highly Destabilizing | 0.035 | N | 0.477 | neutral | None | None | None | None | N |
| P/H | 0.6582 | likely_pathogenic | 0.6914 | pathogenic | -1.546 | Destabilizing | 0.791 | D | 0.647 | neutral | None | None | None | None | N |
| P/I | 0.3355 | likely_benign | 0.3718 | ambiguous | -0.597 | Destabilizing | 0.149 | N | 0.699 | prob.neutral | None | None | None | None | N |
| P/K | 0.7794 | likely_pathogenic | 0.8019 | pathogenic | -1.444 | Destabilizing | 0.149 | N | 0.588 | neutral | None | None | None | None | N |
| P/L | 0.2791 | likely_benign | 0.327 | benign | -0.597 | Destabilizing | 0.027 | N | 0.557 | neutral | N | 0.394995018 | None | None | N |
| P/M | 0.462 | ambiguous | 0.5047 | ambiguous | -0.502 | Destabilizing | 0.555 | D | 0.655 | neutral | None | None | None | None | N |
| P/N | 0.7009 | likely_pathogenic | 0.7154 | pathogenic | -1.354 | Destabilizing | 0.555 | D | 0.68 | prob.neutral | None | None | None | None | N |
| P/Q | 0.5845 | likely_pathogenic | 0.6194 | pathogenic | -1.411 | Destabilizing | 0.484 | N | 0.657 | neutral | N | 0.465127107 | None | None | N |
| P/R | 0.6792 | likely_pathogenic | 0.709 | pathogenic | -1.013 | Destabilizing | 0.317 | N | 0.68 | prob.neutral | N | 0.476344178 | None | None | N |
| P/S | 0.2237 | likely_benign | 0.2433 | benign | -1.928 | Destabilizing | 0.027 | N | 0.441 | neutral | N | 0.451216447 | None | None | N |
| P/T | 0.1684 | likely_benign | 0.1915 | benign | -1.728 | Destabilizing | 0.001 | N | 0.291 | neutral | N | 0.454352752 | None | None | N |
| P/V | 0.1744 | likely_benign | 0.1876 | benign | -0.907 | Destabilizing | 0.035 | N | 0.508 | neutral | None | None | None | None | N |
| P/W | 0.8998 | likely_pathogenic | 0.9006 | pathogenic | -1.343 | Destabilizing | 0.935 | D | 0.681 | prob.neutral | None | None | None | None | N |
| P/Y | 0.7152 | likely_pathogenic | 0.7236 | pathogenic | -1.023 | Destabilizing | 0.555 | D | 0.689 | prob.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.