Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9456 | 28591;28592;28593 | chr2:178710731;178710730;178710729 | chr2:179575458;179575457;179575456 |
| N2AB | 9139 | 27640;27641;27642 | chr2:178710731;178710730;178710729 | chr2:179575458;179575457;179575456 |
| N2A | 8212 | 24859;24860;24861 | chr2:178710731;178710730;178710729 | chr2:179575458;179575457;179575456 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1185144865  |
-2.721 | 0.01 | None | 0.45 | 0.373 | 0.591201240261 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.56E-05 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs1185144865 |
-2.721 | 0.01 | None | 0.45 | 0.373 | 0.591201240261 | gnomAD-4.0.0 | 1.59117E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77254E-05 | None | 0 | 0 | 0 | 0 | 0 |
| V/F | rs772549192 |
-1.738 | 0.055 | None | 0.661 | 0.247 | 0.607789150232 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| V/F | rs772549192 |
-1.738 | 0.055 | None | 0.661 | 0.247 | 0.607789150232 | gnomAD-4.0.0 | 4.80129E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25001E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.679 | likely_pathogenic | 0.7674 | pathogenic | -2.485 | Highly Destabilizing | 0.01 | N | 0.45 | neutral | None | None | None | None | N |
| V/C | 0.9241 | likely_pathogenic | 0.9245 | pathogenic | -2.158 | Highly Destabilizing | 0.628 | D | 0.757 | deleterious | None | None | None | None | N |
| V/D | 0.9637 | likely_pathogenic | 0.9791 | pathogenic | -3.233 | Highly Destabilizing | 0.106 | N | 0.776 | deleterious | None | None | None | None | N |
| V/E | 0.933 | likely_pathogenic | 0.9624 | pathogenic | -2.961 | Highly Destabilizing | 0.136 | N | 0.728 | prob.delet. | None | None | None | None | N |
| V/F | 0.3632 | ambiguous | 0.3281 | benign | -1.462 | Destabilizing | 0.055 | N | 0.661 | neutral | None | None | None | None | N |
| V/G | 0.8326 | likely_pathogenic | 0.8947 | pathogenic | -3.084 | Highly Destabilizing | 0.106 | N | 0.723 | prob.delet. | None | None | None | None | N |
| V/H | 0.9551 | likely_pathogenic | 0.971 | pathogenic | -2.833 | Highly Destabilizing | 0.864 | D | 0.836 | deleterious | None | None | None | None | N |
| V/I | 0.0585 | likely_benign | 0.0541 | benign | -0.773 | Destabilizing | None | N | 0.264 | neutral | None | None | None | None | N |
| V/K | 0.9386 | likely_pathogenic | 0.9688 | pathogenic | -2.159 | Highly Destabilizing | 0.136 | N | 0.733 | prob.delet. | None | None | None | None | N |
| V/L | 0.1919 | likely_benign | 0.2062 | benign | -0.773 | Destabilizing | 0.001 | N | 0.369 | neutral | None | None | None | None | N |
| V/M | 0.2626 | likely_benign | 0.2517 | benign | -0.93 | Destabilizing | 0.214 | N | 0.635 | neutral | None | None | None | None | N |
| V/N | 0.8768 | likely_pathogenic | 0.921 | pathogenic | -2.652 | Highly Destabilizing | 0.356 | N | 0.799 | deleterious | None | None | None | None | N |
| V/P | 0.9621 | likely_pathogenic | 0.979 | pathogenic | -1.32 | Destabilizing | 0.628 | D | 0.781 | deleterious | None | None | None | None | N |
| V/Q | 0.919 | likely_pathogenic | 0.9597 | pathogenic | -2.4 | Highly Destabilizing | 0.628 | D | 0.819 | deleterious | None | None | None | None | N |
| V/R | 0.8986 | likely_pathogenic | 0.9492 | pathogenic | -2.034 | Highly Destabilizing | 0.356 | N | 0.809 | deleterious | None | None | None | None | N |
| V/S | 0.8088 | likely_pathogenic | 0.8709 | pathogenic | -3.293 | Highly Destabilizing | 0.038 | N | 0.69 | prob.neutral | None | None | None | None | N |
| V/T | 0.7797 | likely_pathogenic | 0.8467 | pathogenic | -2.863 | Highly Destabilizing | None | N | 0.315 | neutral | None | None | None | None | N |
| V/W | 0.9658 | likely_pathogenic | 0.9662 | pathogenic | -2.023 | Highly Destabilizing | 0.864 | D | 0.829 | deleterious | None | None | None | None | N |
| V/Y | 0.8671 | likely_pathogenic | 0.8861 | pathogenic | -1.689 | Destabilizing | 0.356 | N | 0.721 | 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.