Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24078 | 72457;72458;72459 | chr2:178573900;178573899;178573898 | chr2:179438627;179438626;179438625 |
| N2AB | 22437 | 67534;67535;67536 | chr2:178573900;178573899;178573898 | chr2:179438627;179438626;179438625 |
| N2A | 21510 | 64753;64754;64755 | chr2:178573900;178573899;178573898 | chr2:179438627;179438626;179438625 |
| N2B | 15013 | 45262;45263;45264 | chr2:178573900;178573899;178573898 | chr2:179438627;179438626;179438625 |
| Novex-1 | 15138 | 45637;45638;45639 | chr2:178573900;178573899;178573898 | chr2:179438627;179438626;179438625 |
| Novex-2 | 15205 | 45838;45839;45840 | chr2:178573900;178573899;178573898 | chr2:179438627;179438626;179438625 |
| 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/M | None | None | 0.999 | N | 0.478 | 0.42 | 0.48512917806 | gnomAD-4.0.0 | 6.85314E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00802E-07 | 0 | 0 |
| I/T | None | None | 0.543 | N | 0.303 | 0.461 | 0.636177026368 | gnomAD-4.0.0 | 3.19447E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.87002E-05 | 0 |
| I/V | rs876658080  |
None | 0.941 | D | 0.347 | 0.184 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| I/V | rs876658080 |
None | 0.941 | D | 0.347 | 0.184 | None | gnomAD-4.0.0 | 9.30841E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.27312E-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 | 0.7522 | likely_pathogenic | 0.803 | pathogenic | -2.233 | Highly Destabilizing | 0.992 | D | 0.446 | neutral | None | None | None | None | N |
| I/C | 0.788 | likely_pathogenic | 0.8291 | pathogenic | -1.398 | Destabilizing | 1.0 | D | 0.569 | neutral | None | None | None | None | N |
| I/D | 0.9291 | likely_pathogenic | 0.9533 | pathogenic | -1.939 | Destabilizing | 0.999 | D | 0.705 | prob.neutral | None | None | None | None | N |
| I/E | 0.7777 | likely_pathogenic | 0.8293 | pathogenic | -1.802 | Destabilizing | 0.999 | D | 0.706 | prob.neutral | None | None | None | None | N |
| I/F | 0.2256 | likely_benign | 0.2552 | benign | -1.379 | Destabilizing | 1.0 | D | 0.453 | neutral | None | None | None | None | N |
| I/G | 0.8705 | likely_pathogenic | 0.9084 | pathogenic | -2.709 | Highly Destabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | N |
| I/H | 0.7539 | likely_pathogenic | 0.8036 | pathogenic | -1.997 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| I/K | 0.5194 | ambiguous | 0.5718 | pathogenic | -1.585 | Destabilizing | 0.998 | D | 0.706 | prob.neutral | D | 0.526730821 | None | None | N |
| I/L | 0.1692 | likely_benign | 0.1987 | benign | -0.911 | Destabilizing | 0.973 | D | 0.325 | neutral | N | 0.49116374 | None | None | N |
| I/M | 0.1077 | likely_benign | 0.1174 | benign | -0.727 | Destabilizing | 0.999 | D | 0.478 | neutral | N | 0.492266603 | None | None | N |
| I/N | 0.5596 | ambiguous | 0.6293 | pathogenic | -1.633 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | N |
| I/P | 0.9457 | likely_pathogenic | 0.9608 | pathogenic | -1.327 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/Q | 0.6444 | likely_pathogenic | 0.6964 | pathogenic | -1.634 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/R | 0.4696 | ambiguous | 0.5331 | ambiguous | -1.157 | Destabilizing | 0.998 | D | 0.727 | prob.delet. | D | 0.549861505 | None | None | N |
| I/S | 0.6912 | likely_pathogenic | 0.7522 | pathogenic | -2.36 | Highly Destabilizing | 0.983 | D | 0.565 | neutral | None | None | None | None | N |
| I/T | 0.6085 | likely_pathogenic | 0.6661 | pathogenic | -2.084 | Highly Destabilizing | 0.543 | D | 0.303 | neutral | N | 0.52045017 | None | None | N |
| I/V | 0.1313 | likely_benign | 0.1527 | benign | -1.327 | Destabilizing | 0.941 | D | 0.347 | neutral | D | 0.532651325 | None | None | N |
| I/W | 0.7457 | likely_pathogenic | 0.7963 | pathogenic | -1.627 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| I/Y | 0.5261 | ambiguous | 0.5856 | pathogenic | -1.36 | Destabilizing | 1.0 | D | 0.563 | neutral | 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.