Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15785 | 47578;47579;47580 | chr2:178617998;178617997;178617996 | chr2:179482725;179482724;179482723 |
| N2AB | 14144 | 42655;42656;42657 | chr2:178617998;178617997;178617996 | chr2:179482725;179482724;179482723 |
| N2A | 13217 | 39874;39875;39876 | chr2:178617998;178617997;178617996 | chr2:179482725;179482724;179482723 |
| N2B | 6720 | 20383;20384;20385 | chr2:178617998;178617997;178617996 | chr2:179482725;179482724;179482723 |
| Novex-1 | 6845 | 20758;20759;20760 | chr2:178617998;178617997;178617996 | chr2:179482725;179482724;179482723 |
| Novex-2 | 6912 | 20959;20960;20961 | chr2:178617998;178617997;178617996 | chr2:179482725;179482724;179482723 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | rs752599239  |
-0.674 | 1.0 | D | 0.761 | 0.551 | 0.454987352986 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 1.29282E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs767824127 |
-0.583 | 1.0 | D | 0.427 | 0.313 | 0.330331372229 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs767824127 |
-0.583 | 1.0 | D | 0.427 | 0.313 | 0.330331372229 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/E | rs767824127 |
-0.583 | 1.0 | D | 0.427 | 0.313 | 0.330331372229 | gnomAD-4.0.0 | 6.58423E-06 | None | None | None | None | I | None | 2.41453E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs755971270 |
-0.899 | 1.0 | N | 0.728 | 0.35 | 0.318828661733 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| D/N | rs755971270 |
-0.899 | 1.0 | N | 0.728 | 0.35 | 0.318828661733 | gnomAD-4.0.0 | 1.59362E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86256E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7804 | likely_pathogenic | 0.7526 | pathogenic | -0.815 | Destabilizing | 1.0 | D | 0.761 | deleterious | D | 0.608297157 | None | None | I |
| D/C | 0.9595 | likely_pathogenic | 0.9502 | pathogenic | -0.327 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| D/E | 0.8276 | likely_pathogenic | 0.7563 | pathogenic | -0.695 | Destabilizing | 1.0 | D | 0.427 | neutral | D | 0.572976697 | None | None | I |
| D/F | 0.9642 | likely_pathogenic | 0.9608 | pathogenic | -0.474 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | I |
| D/G | 0.7277 | likely_pathogenic | 0.7201 | pathogenic | -1.165 | Destabilizing | 1.0 | D | 0.747 | deleterious | D | 0.643237431 | None | None | I |
| D/H | 0.8072 | likely_pathogenic | 0.8105 | pathogenic | -0.797 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | D | 0.65655948 | None | None | I |
| D/I | 0.9468 | likely_pathogenic | 0.9338 | pathogenic | 0.118 | Stabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| D/K | 0.9216 | likely_pathogenic | 0.9071 | pathogenic | -0.493 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | I |
| D/L | 0.9231 | likely_pathogenic | 0.913 | pathogenic | 0.118 | Stabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| D/M | 0.9816 | likely_pathogenic | 0.9732 | pathogenic | 0.644 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| D/N | 0.1947 | likely_benign | 0.1868 | benign | -0.912 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | N | 0.518379131 | None | None | I |
| D/P | 0.9389 | likely_pathogenic | 0.9402 | pathogenic | -0.169 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | I |
| D/Q | 0.9143 | likely_pathogenic | 0.8842 | pathogenic | -0.781 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| D/R | 0.901 | likely_pathogenic | 0.8888 | pathogenic | -0.368 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | I |
| D/S | 0.4446 | ambiguous | 0.3993 | ambiguous | -1.206 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | I |
| D/T | 0.742 | likely_pathogenic | 0.6796 | pathogenic | -0.912 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | I |
| D/V | 0.8728 | likely_pathogenic | 0.8492 | pathogenic | -0.169 | Destabilizing | 1.0 | D | 0.757 | deleterious | D | 0.634753253 | None | None | I |
| D/W | 0.9922 | likely_pathogenic | 0.9917 | pathogenic | -0.271 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | I |
| D/Y | 0.8039 | likely_pathogenic | 0.7959 | pathogenic | -0.225 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | D | 0.724950889 | None | None | I |
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.