Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35188 | 105787;105788;105789 | chr2:178531053;178531052;178531051 | chr2:179395780;179395779;179395778 |
| N2AB | 33547 | 100864;100865;100866 | chr2:178531053;178531052;178531051 | chr2:179395780;179395779;179395778 |
| N2A | 32620 | 98083;98084;98085 | chr2:178531053;178531052;178531051 | chr2:179395780;179395779;179395778 |
| N2B | 26123 | 78592;78593;78594 | chr2:178531053;178531052;178531051 | chr2:179395780;179395779;179395778 |
| Novex-1 | 26248 | 78967;78968;78969 | chr2:178531053;178531052;178531051 | chr2:179395780;179395779;179395778 |
| Novex-2 | 26315 | 79168;79169;79170 | chr2:178531053;178531052;178531051 | chr2:179395780;179395779;179395778 |
| 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/L | rs727504491  |
-0.702 | 0.983 | D | 0.421 | 0.677 | 0.718028692739 | gnomAD-2.1.1 | 2.49E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.67E-05 | 1.40056E-04 |
| I/L | rs727504491 |
-0.702 | 0.983 | D | 0.421 | 0.677 | 0.718028692739 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 4.41E-05 | 0 | 0 |
| I/L | rs727504491 |
-0.702 | 0.983 | D | 0.421 | 0.677 | 0.718028692739 | gnomAD-4.0.0 | 2.54028E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.64962E-03 | 2.37312E-05 | 1.09791E-05 | 3.20061E-05 |
| I/M | None | None | 0.999 | D | 0.769 | 0.507 | 0.633405343067 | gnomAD-4.0.0 | 1.59089E-06 | None | None | None | None | N | None | 5.65291E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs764963502 |
-2.724 | 0.999 | D | 0.838 | 0.853 | 0.866247393669 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/T | rs764963502 |
-2.724 | 0.999 | D | 0.838 | 0.853 | 0.866247393669 | gnomAD-4.0.0 | 3.18176E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86541E-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 | 0.9424 | likely_pathogenic | 0.965 | pathogenic | -3.103 | Highly Destabilizing | 0.998 | D | 0.717 | prob.delet. | None | None | None | None | N |
| I/C | 0.9648 | likely_pathogenic | 0.9764 | pathogenic | -2.89 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| I/D | 0.9917 | likely_pathogenic | 0.9956 | pathogenic | -3.594 | Highly Destabilizing | 0.999 | D | 0.898 | deleterious | None | None | None | None | N |
| I/E | 0.986 | likely_pathogenic | 0.9915 | pathogenic | -3.361 | Highly Destabilizing | 0.999 | D | 0.899 | deleterious | None | None | None | None | N |
| I/F | 0.3597 | ambiguous | 0.4547 | ambiguous | -1.931 | Destabilizing | 0.999 | D | 0.824 | deleterious | D | 0.573882001 | None | None | N |
| I/G | 0.9875 | likely_pathogenic | 0.9933 | pathogenic | -3.665 | Highly Destabilizing | 0.999 | D | 0.899 | deleterious | None | None | None | None | N |
| I/H | 0.969 | likely_pathogenic | 0.9832 | pathogenic | -2.916 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| I/K | 0.9584 | likely_pathogenic | 0.9763 | pathogenic | -2.49 | Highly Destabilizing | 0.999 | D | 0.899 | deleterious | None | None | None | None | N |
| I/L | 0.2506 | likely_benign | 0.3043 | benign | -1.452 | Destabilizing | 0.983 | D | 0.421 | neutral | D | 0.566522946 | None | None | N |
| I/M | 0.2059 | likely_benign | 0.2543 | benign | -1.633 | Destabilizing | 0.999 | D | 0.769 | deleterious | D | 0.581371991 | None | None | N |
| I/N | 0.9056 | likely_pathogenic | 0.9466 | pathogenic | -2.937 | Highly Destabilizing | 0.999 | D | 0.915 | deleterious | D | 0.652201852 | None | None | N |
| I/P | 0.996 | likely_pathogenic | 0.9978 | pathogenic | -1.987 | Destabilizing | 0.999 | D | 0.909 | deleterious | None | None | None | None | N |
| I/Q | 0.9706 | likely_pathogenic | 0.9824 | pathogenic | -2.815 | Highly Destabilizing | 1.0 | D | 0.924 | deleterious | None | None | None | None | N |
| I/R | 0.9461 | likely_pathogenic | 0.969 | pathogenic | -2.079 | Highly Destabilizing | 0.999 | D | 0.913 | deleterious | None | None | None | None | N |
| I/S | 0.9413 | likely_pathogenic | 0.9658 | pathogenic | -3.683 | Highly Destabilizing | 0.999 | D | 0.887 | deleterious | D | 0.636182491 | None | None | N |
| I/T | 0.9389 | likely_pathogenic | 0.9639 | pathogenic | -3.296 | Highly Destabilizing | 0.999 | D | 0.838 | deleterious | D | 0.635778882 | None | None | N |
| I/V | 0.2313 | likely_benign | 0.2528 | benign | -1.987 | Destabilizing | 0.983 | D | 0.385 | neutral | D | 0.539916318 | None | None | N |
| I/W | 0.9598 | likely_pathogenic | 0.9727 | pathogenic | -2.251 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| I/Y | 0.8344 | likely_pathogenic | 0.8861 | pathogenic | -2.082 | Highly Destabilizing | 0.999 | D | 0.844 | 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.