Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21709 | 65350;65351;65352 | chr2:178584426;178584425;178584424 | chr2:179449153;179449152;179449151 |
| N2AB | 20068 | 60427;60428;60429 | chr2:178584426;178584425;178584424 | chr2:179449153;179449152;179449151 |
| N2A | 19141 | 57646;57647;57648 | chr2:178584426;178584425;178584424 | chr2:179449153;179449152;179449151 |
| N2B | 12644 | 38155;38156;38157 | chr2:178584426;178584425;178584424 | chr2:179449153;179449152;179449151 |
| Novex-1 | 12769 | 38530;38531;38532 | chr2:178584426;178584425;178584424 | chr2:179449153;179449152;179449151 |
| Novex-2 | 12836 | 38731;38732;38733 | chr2:178584426;178584425;178584424 | chr2:179449153;179449152;179449151 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | rs549711049  |
-0.523 | 1.0 | N | 0.763 | 0.348 | 0.418718287753 | gnomAD-2.1.1 | 5.24E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 4.24892E-04 | None | 0 | 0 | 0 |
| A/P | rs549711049 |
-0.523 | 1.0 | N | 0.763 | 0.348 | 0.418718287753 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 6.21118E-04 | 0 |
| A/P | rs549711049 |
-0.523 | 1.0 | N | 0.763 | 0.348 | 0.418718287753 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| A/P | rs549711049 |
-0.523 | 1.0 | N | 0.763 | 0.348 | 0.418718287753 | gnomAD-4.0.0 | 2.23145E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.95326E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5649 | likely_pathogenic | 0.5208 | ambiguous | -0.939 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| A/D | 0.9234 | likely_pathogenic | 0.8852 | pathogenic | -1.544 | Destabilizing | 0.999 | D | 0.753 | deleterious | N | 0.480091744 | None | None | I |
| A/E | 0.8545 | likely_pathogenic | 0.785 | pathogenic | -1.518 | Destabilizing | 0.999 | D | 0.749 | deleterious | None | None | None | None | I |
| A/F | 0.8661 | likely_pathogenic | 0.8179 | pathogenic | -1.014 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| A/G | 0.384 | ambiguous | 0.337 | benign | -1.363 | Destabilizing | 0.996 | D | 0.564 | neutral | N | 0.469749396 | None | None | I |
| A/H | 0.9411 | likely_pathogenic | 0.9233 | pathogenic | -1.661 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | I |
| A/I | 0.5646 | likely_pathogenic | 0.472 | ambiguous | -0.273 | Destabilizing | 0.998 | D | 0.76 | deleterious | None | None | None | None | I |
| A/K | 0.9794 | likely_pathogenic | 0.966 | pathogenic | -1.306 | Destabilizing | 0.998 | D | 0.757 | deleterious | None | None | None | None | I |
| A/L | 0.5211 | ambiguous | 0.4556 | ambiguous | -0.273 | Destabilizing | 0.994 | D | 0.648 | neutral | None | None | None | None | I |
| A/M | 0.5758 | likely_pathogenic | 0.4954 | ambiguous | -0.216 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| A/N | 0.8411 | likely_pathogenic | 0.7795 | pathogenic | -1.112 | Destabilizing | 0.999 | D | 0.761 | deleterious | None | None | None | None | I |
| A/P | 0.9482 | likely_pathogenic | 0.925 | pathogenic | -0.485 | Destabilizing | 1.0 | D | 0.763 | deleterious | N | 0.487346672 | None | None | I |
| A/Q | 0.8605 | likely_pathogenic | 0.8072 | pathogenic | -1.19 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | I |
| A/R | 0.961 | likely_pathogenic | 0.9424 | pathogenic | -1.065 | Destabilizing | 0.999 | D | 0.775 | deleterious | None | None | None | None | I |
| A/S | 0.2351 | likely_benign | 0.201 | benign | -1.484 | Destabilizing | 0.984 | D | 0.539 | neutral | N | 0.512958339 | None | None | I |
| A/T | 0.2666 | likely_benign | 0.1967 | benign | -1.358 | Destabilizing | 0.79 | D | 0.399 | neutral | N | 0.502375986 | None | None | I |
| A/V | 0.2676 | likely_benign | 0.2052 | benign | -0.485 | Destabilizing | 0.992 | D | 0.573 | neutral | N | 0.413679566 | None | None | I |
| A/W | 0.9768 | likely_pathogenic | 0.968 | pathogenic | -1.491 | Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | I |
| A/Y | 0.9248 | likely_pathogenic | 0.8969 | pathogenic | -1.039 | Destabilizing | 1.0 | D | 0.787 | deleterious | 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.