Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17899 | 53920;53921;53922 | chr2:178605600;178605599;178605598 | chr2:179470327;179470326;179470325 |
| N2AB | 16258 | 48997;48998;48999 | chr2:178605600;178605599;178605598 | chr2:179470327;179470326;179470325 |
| N2A | 15331 | 46216;46217;46218 | chr2:178605600;178605599;178605598 | chr2:179470327;179470326;179470325 |
| N2B | 8834 | 26725;26726;26727 | chr2:178605600;178605599;178605598 | chr2:179470327;179470326;179470325 |
| Novex-1 | 8959 | 27100;27101;27102 | chr2:178605600;178605599;178605598 | chr2:179470327;179470326;179470325 |
| Novex-2 | 9026 | 27301;27302;27303 | chr2:178605600;178605599;178605598 | chr2:179470327;179470326;179470325 |
| 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 | rs369723141  |
None | 0.939 | D | 0.69 | 0.541 | 0.850888709144 | gnomAD-4.0.0 | 1.59444E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86508E-06 | 0 | 0 |
| I/V | rs1359912614 |
-2.164 | 0.02 | N | 0.199 | 0.092 | 0.38225645794 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 2.87687E-04 | 0 | 0 |
| I/V | rs1359912614 |
-2.164 | 0.02 | N | 0.199 | 0.092 | 0.38225645794 | gnomAD-3.1.2 | 6.6E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.44E-05 | 0 | 0 | 0 | 0 |
| I/V | rs1359912614 |
-2.164 | 0.02 | N | 0.199 | 0.092 | 0.38225645794 | gnomAD-4.0.0 | 3.85763E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 4.72233E-05 | 0 | 0 | 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 | 0.913 | likely_pathogenic | 0.8593 | pathogenic | -3.145 | Highly Destabilizing | 0.91 | D | 0.678 | prob.neutral | None | None | None | None | N |
| I/C | 0.9694 | likely_pathogenic | 0.9581 | pathogenic | -2.292 | Highly Destabilizing | 0.999 | D | 0.761 | deleterious | None | None | None | None | N |
| I/D | 0.9996 | likely_pathogenic | 0.9994 | pathogenic | -3.893 | Highly Destabilizing | 0.998 | D | 0.897 | deleterious | None | None | None | None | N |
| I/E | 0.9982 | likely_pathogenic | 0.9971 | pathogenic | -3.576 | Highly Destabilizing | 0.993 | D | 0.895 | deleterious | None | None | None | None | N |
| I/F | 0.8793 | likely_pathogenic | 0.8367 | pathogenic | -1.882 | Destabilizing | 0.982 | D | 0.646 | neutral | N | 0.51160449 | None | None | N |
| I/G | 0.9957 | likely_pathogenic | 0.9926 | pathogenic | -3.738 | Highly Destabilizing | 0.993 | D | 0.888 | deleterious | None | None | None | None | N |
| I/H | 0.9986 | likely_pathogenic | 0.9978 | pathogenic | -3.303 | Highly Destabilizing | 0.999 | D | 0.888 | deleterious | None | None | None | None | N |
| I/K | 0.9972 | likely_pathogenic | 0.9963 | pathogenic | -2.557 | Highly Destabilizing | 0.993 | D | 0.896 | deleterious | None | None | None | None | N |
| I/L | 0.3145 | likely_benign | 0.259 | benign | -1.346 | Destabilizing | 0.58 | D | 0.323 | neutral | N | 0.476907112 | None | None | N |
| I/M | 0.5361 | ambiguous | 0.4377 | ambiguous | -1.469 | Destabilizing | 0.991 | D | 0.64 | neutral | D | 0.530245738 | None | None | N |
| I/N | 0.9953 | likely_pathogenic | 0.9928 | pathogenic | -3.27 | Highly Destabilizing | 0.997 | D | 0.912 | deleterious | D | 0.523378869 | None | None | N |
| I/P | 0.9947 | likely_pathogenic | 0.9928 | pathogenic | -1.94 | Destabilizing | 0.998 | D | 0.901 | deleterious | None | None | None | None | N |
| I/Q | 0.9972 | likely_pathogenic | 0.9959 | pathogenic | -2.945 | Highly Destabilizing | 0.998 | D | 0.911 | deleterious | None | None | None | None | N |
| I/R | 0.9949 | likely_pathogenic | 0.9929 | pathogenic | -2.459 | Highly Destabilizing | 0.993 | D | 0.911 | deleterious | None | None | None | None | N |
| I/S | 0.9859 | likely_pathogenic | 0.9769 | pathogenic | -3.807 | Highly Destabilizing | 0.991 | D | 0.826 | deleterious | D | 0.523378869 | None | None | N |
| I/T | 0.8849 | likely_pathogenic | 0.8162 | pathogenic | -3.337 | Highly Destabilizing | 0.939 | D | 0.69 | prob.neutral | D | 0.52312538 | None | None | N |
| I/V | 0.0905 | likely_benign | 0.083 | benign | -1.94 | Destabilizing | 0.02 | N | 0.199 | neutral | N | 0.397493818 | None | None | N |
| I/W | 0.9982 | likely_pathogenic | 0.9971 | pathogenic | -2.296 | Highly Destabilizing | 0.999 | D | 0.857 | deleterious | None | None | None | None | N |
| I/Y | 0.9945 | likely_pathogenic | 0.9918 | pathogenic | -2.145 | Highly Destabilizing | 0.993 | D | 0.751 | 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.