Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15795 | 47608;47609;47610 | chr2:178617968;178617967;178617966 | chr2:179482695;179482694;179482693 |
| N2AB | 14154 | 42685;42686;42687 | chr2:178617968;178617967;178617966 | chr2:179482695;179482694;179482693 |
| N2A | 13227 | 39904;39905;39906 | chr2:178617968;178617967;178617966 | chr2:179482695;179482694;179482693 |
| N2B | 6730 | 20413;20414;20415 | chr2:178617968;178617967;178617966 | chr2:179482695;179482694;179482693 |
| Novex-1 | 6855 | 20788;20789;20790 | chr2:178617968;178617967;178617966 | chr2:179482695;179482694;179482693 |
| Novex-2 | 6922 | 20989;20990;20991 | chr2:178617968;178617967;178617966 | chr2:179482695;179482694;179482693 |
| 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 | rs370625853  |
-3.579 | 0.896 | D | 0.635 | 0.451 | None | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 6.46E-05 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs370625853 |
-3.579 | 0.896 | D | 0.635 | 0.451 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 1.31423E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs370625853 |
-3.579 | 0.896 | D | 0.635 | 0.451 | None | gnomAD-4.0.0 | 1.02641E-05 | None | None | None | None | N | None | 0 | 6.79002E-05 | None | 0 | 0 | None | 0 | 0 | 7.19055E-06 | 1.34055E-05 | 0 |
| I/V | rs750870811 |
-1.937 | 0.004 | N | 0.198 | 0.05 | 0.466230903105 | gnomAD-2.1.1 | 3.63E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.02E-05 | 0 |
| I/V | rs750870811 |
-1.937 | 0.004 | N | 0.198 | 0.05 | 0.466230903105 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs750870811 |
-1.937 | 0.004 | N | 0.198 | 0.05 | 0.466230903105 | gnomAD-4.0.0 | 9.30212E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.27214E-05 | 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 | 0.9065 | likely_pathogenic | 0.8803 | pathogenic | -3.047 | Highly Destabilizing | 0.702 | D | 0.674 | neutral | None | None | None | None | N |
| I/C | 0.9738 | likely_pathogenic | 0.9645 | pathogenic | -2.441 | Highly Destabilizing | 0.999 | D | 0.793 | deleterious | None | None | None | None | N |
| I/D | 0.9994 | likely_pathogenic | 0.9994 | pathogenic | -3.82 | Highly Destabilizing | 0.996 | D | 0.861 | deleterious | None | None | None | None | N |
| I/E | 0.9972 | likely_pathogenic | 0.997 | pathogenic | -3.541 | Highly Destabilizing | 0.988 | D | 0.843 | deleterious | None | None | None | None | N |
| I/F | 0.7383 | likely_pathogenic | 0.7343 | pathogenic | -1.798 | Destabilizing | 0.968 | D | 0.629 | neutral | D | 0.741094739 | None | None | N |
| I/G | 0.9933 | likely_pathogenic | 0.9914 | pathogenic | -3.635 | Highly Destabilizing | 0.988 | D | 0.814 | deleterious | None | None | None | None | N |
| I/H | 0.9979 | likely_pathogenic | 0.9976 | pathogenic | -3.17 | Highly Destabilizing | 0.999 | D | 0.871 | deleterious | None | None | None | None | N |
| I/K | 0.9947 | likely_pathogenic | 0.9946 | pathogenic | -2.558 | Highly Destabilizing | 0.988 | D | 0.845 | deleterious | None | None | None | None | N |
| I/L | 0.2793 | likely_benign | 0.2529 | benign | -1.294 | Destabilizing | 0.437 | N | 0.316 | neutral | N | 0.485041815 | None | None | N |
| I/M | 0.3517 | ambiguous | 0.3286 | benign | -1.351 | Destabilizing | 0.984 | D | 0.621 | neutral | D | 0.620644329 | None | None | N |
| I/N | 0.9939 | likely_pathogenic | 0.9933 | pathogenic | -3.108 | Highly Destabilizing | 0.995 | D | 0.875 | deleterious | D | 0.742333682 | None | None | N |
| I/P | 0.9964 | likely_pathogenic | 0.9956 | pathogenic | -1.866 | Destabilizing | 0.996 | D | 0.865 | deleterious | None | None | None | None | N |
| I/Q | 0.9951 | likely_pathogenic | 0.9946 | pathogenic | -2.873 | Highly Destabilizing | 0.996 | D | 0.88 | deleterious | None | None | None | None | N |
| I/R | 0.9909 | likely_pathogenic | 0.9901 | pathogenic | -2.302 | Highly Destabilizing | 0.988 | D | 0.873 | deleterious | None | None | None | None | N |
| I/S | 0.9809 | likely_pathogenic | 0.9751 | pathogenic | -3.736 | Highly Destabilizing | 0.984 | D | 0.789 | deleterious | D | 0.742333682 | None | None | N |
| I/T | 0.8714 | likely_pathogenic | 0.8299 | pathogenic | -3.308 | Highly Destabilizing | 0.896 | D | 0.635 | neutral | D | 0.741094739 | None | None | N |
| I/V | 0.1096 | likely_benign | 0.0949 | benign | -1.866 | Destabilizing | 0.004 | N | 0.198 | neutral | N | 0.434709153 | None | None | N |
| I/W | 0.9953 | likely_pathogenic | 0.9952 | pathogenic | -2.298 | Highly Destabilizing | 0.999 | D | 0.855 | deleterious | None | None | None | None | N |
| I/Y | 0.9843 | likely_pathogenic | 0.9842 | pathogenic | -2.08 | Highly Destabilizing | 0.988 | D | 0.754 | 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.