Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6184 | 18775;18776;18777 | chr2:178729703;178729702;178729701 | chr2:179594430;179594429;179594428 |
| N2AB | 5867 | 17824;17825;17826 | chr2:178729703;178729702;178729701 | chr2:179594430;179594429;179594428 |
| N2A | 4940 | 15043;15044;15045 | chr2:178729703;178729702;178729701 | chr2:179594430;179594429;179594428 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/S | None | None | 1.0 | N | 0.634 | 0.415 | 0.411133732114 | gnomAD-4.0.0 | 1.36848E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79903E-06 | 0 | 0 |
| A/T | rs72648947  |
-0.152 | 1.0 | D | 0.711 | 0.423 | None | gnomAD-2.1.1 | 3.82553E-04 | None | None | None | None | I | None | 1.24069E-04 | 6.22383E-04 | None | 0 | 0 | None | 1.63399E-04 | None | 1.19894E-04 | 5.64254E-04 | 2.81057E-04 |
| A/T | rs72648947 |
-0.152 | 1.0 | D | 0.711 | 0.423 | None | gnomAD-3.1.2 | 4.53607E-04 | None | None | None | None | I | None | 4.83E-05 | 2.03199E-03 | 0 | 0 | 0 | None | 9.43E-05 | 6.32911E-03 | 4.85266E-04 | 0 | 0 |
| A/T | rs72648947 |
-0.152 | 1.0 | D | 0.711 | 0.423 | None | gnomAD-4.0.0 | 3.69336E-04 | None | None | None | None | I | None | 1.06644E-04 | 9.0003E-04 | None | 0 | 2.22886E-05 | None | 2.65584E-04 | 3.63396E-03 | 3.83993E-04 | 1.64694E-04 | 4.16173E-04 |
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 | 0.6764 | likely_pathogenic | 0.6773 | pathogenic | -0.712 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| A/D | 0.6802 | likely_pathogenic | 0.6453 | pathogenic | -0.62 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | I |
| A/E | 0.6113 | likely_pathogenic | 0.5873 | pathogenic | -0.786 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.505877861 | None | None | I |
| A/F | 0.4393 | ambiguous | 0.4081 | ambiguous | -0.942 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | I |
| A/G | 0.2482 | likely_benign | 0.2912 | benign | -0.216 | Destabilizing | 1.0 | D | 0.599 | neutral | N | 0.511687531 | None | None | I |
| A/H | 0.7746 | likely_pathogenic | 0.7476 | pathogenic | -0.255 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
| A/I | 0.3329 | likely_benign | 0.3184 | benign | -0.375 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| A/K | 0.8452 | likely_pathogenic | 0.8298 | pathogenic | -0.562 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| A/L | 0.3681 | ambiguous | 0.3621 | ambiguous | -0.375 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| A/M | 0.3802 | ambiguous | 0.384 | ambiguous | -0.414 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| A/N | 0.5946 | likely_pathogenic | 0.5803 | pathogenic | -0.212 | Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | I |
| A/P | 0.9076 | likely_pathogenic | 0.9099 | pathogenic | -0.29 | Destabilizing | 1.0 | D | 0.741 | deleterious | D | 0.537909315 | None | None | I |
| A/Q | 0.6919 | likely_pathogenic | 0.6737 | pathogenic | -0.522 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | I |
| A/R | 0.7313 | likely_pathogenic | 0.7113 | pathogenic | -0.074 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| A/S | 0.1364 | likely_benign | 0.1442 | benign | -0.363 | Destabilizing | 1.0 | D | 0.634 | neutral | N | 0.504103434 | None | None | I |
| A/T | 0.1594 | likely_benign | 0.2203 | benign | -0.461 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | D | 0.534613952 | None | None | I |
| A/V | 0.1473 | likely_benign | 0.1425 | benign | -0.29 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | N | 0.489113979 | None | None | I |
| A/W | 0.8903 | likely_pathogenic | 0.8688 | pathogenic | -1.056 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| A/Y | 0.7003 | likely_pathogenic | 0.6681 | pathogenic | -0.719 | Destabilizing | 1.0 | D | 0.792 | 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.