Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19139 | 57640;57641;57642 | chr2:178597667;178597666;178597665 | chr2:179462394;179462393;179462392 |
| N2AB | 17498 | 52717;52718;52719 | chr2:178597667;178597666;178597665 | chr2:179462394;179462393;179462392 |
| N2A | 16571 | 49936;49937;49938 | chr2:178597667;178597666;178597665 | chr2:179462394;179462393;179462392 |
| N2B | 10074 | 30445;30446;30447 | chr2:178597667;178597666;178597665 | chr2:179462394;179462393;179462392 |
| Novex-1 | 10199 | 30820;30821;30822 | chr2:178597667;178597666;178597665 | chr2:179462394;179462393;179462392 |
| Novex-2 | 10266 | 31021;31022;31023 | chr2:178597667;178597666;178597665 | chr2:179462394;179462393;179462392 |
| 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 | rs397517629  |
None | 0.294 | N | 0.431 | 0.151 | 0.401327265625 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/L | rs397517629 |
None | 0.294 | N | 0.431 | 0.151 | 0.401327265625 | gnomAD-4.0.0 | 6.57635E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47085E-05 | 0 | 0 |
| I/T | rs727503591 |
-1.609 | 0.822 | D | 0.507 | 0.437 | None | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.03189E-04 | None | 0 | None | 0 | 7.85E-06 | 0 |
| I/T | rs727503591 |
-1.609 | 0.822 | D | 0.507 | 0.437 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs727503591 |
-1.609 | 0.822 | D | 0.507 | 0.437 | None | gnomAD-4.0.0 | 3.59531E-05 | None | None | None | None | I | None | 1.33543E-05 | 0 | None | 0 | 4.47047E-05 | None | 0 | 0 | 4.57802E-05 | 0 | 1.60143E-05 |
| I/V | None | None | 0.006 | N | 0.226 | 0.069 | 0.311691414656 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.9375E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2144 | likely_benign | 0.2983 | benign | -1.549 | Destabilizing | 0.754 | D | 0.451 | neutral | None | None | None | None | I |
| I/C | 0.7328 | likely_pathogenic | 0.7283 | pathogenic | -0.917 | Destabilizing | 0.998 | D | 0.625 | neutral | None | None | None | None | I |
| I/D | 0.8494 | likely_pathogenic | 0.8986 | pathogenic | -0.655 | Destabilizing | 0.993 | D | 0.753 | deleterious | None | None | None | None | I |
| I/E | 0.549 | ambiguous | 0.6043 | pathogenic | -0.657 | Destabilizing | 0.978 | D | 0.748 | deleterious | None | None | None | None | I |
| I/F | 0.268 | likely_benign | 0.3405 | ambiguous | -1.136 | Destabilizing | 0.942 | D | 0.539 | neutral | N | 0.519378171 | None | None | I |
| I/G | 0.6933 | likely_pathogenic | 0.7768 | pathogenic | -1.862 | Destabilizing | 0.978 | D | 0.734 | prob.delet. | None | None | None | None | I |
| I/H | 0.6683 | likely_pathogenic | 0.7231 | pathogenic | -0.994 | Destabilizing | 0.998 | D | 0.755 | deleterious | None | None | None | None | I |
| I/K | 0.3792 | ambiguous | 0.4403 | ambiguous | -0.863 | Destabilizing | 0.978 | D | 0.749 | deleterious | None | None | None | None | I |
| I/L | 0.1446 | likely_benign | 0.1743 | benign | -0.77 | Destabilizing | 0.294 | N | 0.431 | neutral | N | 0.497117387 | None | None | I |
| I/M | 0.1004 | likely_benign | 0.1167 | benign | -0.609 | Destabilizing | 0.942 | D | 0.549 | neutral | N | 0.521111754 | None | None | I |
| I/N | 0.5019 | ambiguous | 0.5809 | pathogenic | -0.66 | Destabilizing | 0.99 | D | 0.761 | deleterious | N | 0.496977091 | None | None | I |
| I/P | 0.7885 | likely_pathogenic | 0.885 | pathogenic | -0.997 | Destabilizing | 0.993 | D | 0.762 | deleterious | None | None | None | None | I |
| I/Q | 0.4548 | ambiguous | 0.493 | ambiguous | -0.827 | Destabilizing | 0.993 | D | 0.761 | deleterious | None | None | None | None | I |
| I/R | 0.3129 | likely_benign | 0.4079 | ambiguous | -0.294 | Destabilizing | 0.978 | D | 0.76 | deleterious | None | None | None | None | I |
| I/S | 0.3369 | likely_benign | 0.4085 | ambiguous | -1.322 | Destabilizing | 0.942 | D | 0.652 | neutral | N | 0.492595771 | None | None | I |
| I/T | 0.1036 | likely_benign | 0.1328 | benign | -1.197 | Destabilizing | 0.822 | D | 0.507 | neutral | D | 0.526864291 | None | None | I |
| I/V | 0.0586 | likely_benign | 0.0643 | benign | -0.997 | Destabilizing | 0.006 | N | 0.226 | neutral | N | 0.443090901 | None | None | I |
| I/W | 0.8341 | likely_pathogenic | 0.8855 | pathogenic | -1.157 | Destabilizing | 0.998 | D | 0.726 | prob.delet. | None | None | None | None | I |
| I/Y | 0.6752 | likely_pathogenic | 0.7455 | pathogenic | -0.932 | Destabilizing | 0.978 | D | 0.645 | neutral | None | None | 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.