Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22674 | 68245;68246;68247 | chr2:178579010;178579009;178579008 | chr2:179443737;179443736;179443735 |
| N2AB | 21033 | 63322;63323;63324 | chr2:178579010;178579009;178579008 | chr2:179443737;179443736;179443735 |
| N2A | 20106 | 60541;60542;60543 | chr2:178579010;178579009;178579008 | chr2:179443737;179443736;179443735 |
| N2B | 13609 | 41050;41051;41052 | chr2:178579010;178579009;178579008 | chr2:179443737;179443736;179443735 |
| Novex-1 | 13734 | 41425;41426;41427 | chr2:178579010;178579009;178579008 | chr2:179443737;179443736;179443735 |
| Novex-2 | 13801 | 41626;41627;41628 | chr2:178579010;178579009;178579008 | chr2:179443737;179443736;179443735 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/T | rs367642533  |
-0.705 | 0.989 | D | 0.618 | 0.227 | None | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66223E-04 |
| S/T | rs367642533 |
-0.705 | 0.989 | D | 0.618 | 0.227 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | rs367642533 |
-0.705 | 0.989 | D | 0.618 | 0.227 | None | gnomAD-4.0.0 | 3.84615E-06 | None | None | None | None | I | None | 3.38558E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.3946E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1441 | likely_benign | 0.1368 | benign | -0.833 | Destabilizing | 0.333 | N | 0.414 | neutral | N | 0.480155274 | None | None | I |
| S/C | 0.1419 | likely_benign | 0.1475 | benign | -0.579 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | D | 0.52533299 | None | None | I |
| S/D | 0.9499 | likely_pathogenic | 0.9382 | pathogenic | -0.54 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | None | None | None | None | I |
| S/E | 0.9536 | likely_pathogenic | 0.9454 | pathogenic | -0.534 | Destabilizing | 0.996 | D | 0.686 | prob.neutral | None | None | None | None | I |
| S/F | 0.7499 | likely_pathogenic | 0.7293 | pathogenic | -1.014 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | N | 0.50430252 | None | None | I |
| S/G | 0.2245 | likely_benign | 0.1984 | benign | -1.088 | Destabilizing | 0.98 | D | 0.603 | neutral | None | None | None | None | I |
| S/H | 0.8973 | likely_pathogenic | 0.8875 | pathogenic | -1.561 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| S/I | 0.6656 | likely_pathogenic | 0.6625 | pathogenic | -0.257 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | I |
| S/K | 0.9895 | likely_pathogenic | 0.9874 | pathogenic | -0.771 | Destabilizing | 0.996 | D | 0.687 | prob.neutral | None | None | None | None | I |
| S/L | 0.3906 | ambiguous | 0.3727 | ambiguous | -0.257 | Destabilizing | 0.992 | D | 0.655 | neutral | None | None | None | None | I |
| S/M | 0.479 | ambiguous | 0.4668 | ambiguous | 0.112 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| S/N | 0.6775 | likely_pathogenic | 0.6375 | pathogenic | -0.78 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | I |
| S/P | 0.9882 | likely_pathogenic | 0.9843 | pathogenic | -0.416 | Destabilizing | 0.998 | D | 0.697 | prob.neutral | N | 0.51556992 | None | None | I |
| S/Q | 0.9261 | likely_pathogenic | 0.9166 | pathogenic | -0.954 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| S/R | 0.9793 | likely_pathogenic | 0.9749 | pathogenic | -0.649 | Destabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | I |
| S/T | 0.1946 | likely_benign | 0.1925 | benign | -0.776 | Destabilizing | 0.989 | D | 0.618 | neutral | D | 0.522676687 | None | None | I |
| S/V | 0.5048 | ambiguous | 0.5195 | ambiguous | -0.416 | Destabilizing | 0.992 | D | 0.663 | neutral | None | None | None | None | I |
| S/W | 0.8709 | likely_pathogenic | 0.852 | pathogenic | -0.979 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| S/Y | 0.7702 | likely_pathogenic | 0.7349 | pathogenic | -0.717 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | N | 0.51556992 | 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.