Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26059 | 78400;78401;78402 | chr2:178567957;178567956;178567955 | chr2:179432684;179432683;179432682 |
| N2AB | 24418 | 73477;73478;73479 | chr2:178567957;178567956;178567955 | chr2:179432684;179432683;179432682 |
| N2A | 23491 | 70696;70697;70698 | chr2:178567957;178567956;178567955 | chr2:179432684;179432683;179432682 |
| N2B | 16994 | 51205;51206;51207 | chr2:178567957;178567956;178567955 | chr2:179432684;179432683;179432682 |
| Novex-1 | 17119 | 51580;51581;51582 | chr2:178567957;178567956;178567955 | chr2:179432684;179432683;179432682 |
| Novex-2 | 17186 | 51781;51782;51783 | chr2:178567957;178567956;178567955 | chr2:179432684;179432683;179432682 |
| 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/T | rs757758607  |
-2.119 | 1.0 | N | 0.697 | 0.464 | 0.488477830397 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.0536E-04 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs757758607 |
-2.119 | 1.0 | N | 0.697 | 0.464 | 0.488477830397 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93349E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs757758607 |
-2.119 | 1.0 | N | 0.697 | 0.464 | 0.488477830397 | gnomAD-4.0.0 | 6.19787E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.56097E-04 | None | 0 | 1.64636E-04 | 0 | 2.19587E-05 | 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 | 0.3374 | likely_benign | 0.4036 | ambiguous | -1.871 | Destabilizing | 0.999 | D | 0.507 | neutral | None | None | None | None | N |
| I/C | 0.6891 | likely_pathogenic | 0.7079 | pathogenic | -0.943 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| I/D | 0.8458 | likely_pathogenic | 0.896 | pathogenic | -1.521 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| I/E | 0.7428 | likely_pathogenic | 0.8038 | pathogenic | -1.465 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| I/F | 0.2667 | likely_benign | 0.2923 | benign | -1.239 | Destabilizing | 1.0 | D | 0.746 | deleterious | N | 0.51726808 | None | None | N |
| I/G | 0.704 | likely_pathogenic | 0.7824 | pathogenic | -2.25 | Highly Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| I/H | 0.6983 | likely_pathogenic | 0.7506 | pathogenic | -1.483 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| I/K | 0.5944 | likely_pathogenic | 0.667 | pathogenic | -1.234 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| I/L | 0.1069 | likely_benign | 0.1043 | benign | -0.866 | Destabilizing | 0.993 | D | 0.362 | neutral | N | 0.4100819 | None | None | N |
| I/M | 0.0963 | likely_benign | 0.1007 | benign | -0.593 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.484712945 | None | None | N |
| I/N | 0.3611 | ambiguous | 0.4359 | ambiguous | -1.143 | Destabilizing | 1.0 | D | 0.761 | deleterious | N | 0.483443508 | None | None | N |
| I/P | 0.9458 | likely_pathogenic | 0.9625 | pathogenic | -1.173 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| I/Q | 0.6021 | likely_pathogenic | 0.669 | pathogenic | -1.272 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| I/R | 0.4698 | ambiguous | 0.5554 | ambiguous | -0.668 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| I/S | 0.3634 | ambiguous | 0.4461 | ambiguous | -1.768 | Destabilizing | 1.0 | D | 0.755 | deleterious | N | 0.435553561 | None | None | N |
| I/T | 0.1837 | likely_benign | 0.222 | benign | -1.595 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | N | 0.400299263 | None | None | N |
| I/V | 0.0873 | likely_benign | 0.0903 | benign | -1.173 | Destabilizing | 0.993 | D | 0.349 | neutral | N | 0.446655989 | None | None | N |
| I/W | 0.8237 | likely_pathogenic | 0.853 | pathogenic | -1.413 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | N |
| I/Y | 0.6417 | likely_pathogenic | 0.6833 | pathogenic | -1.156 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | 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.