Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22275 | 67048;67049;67050 | chr2:178580556;178580555;178580554 | chr2:179445283;179445282;179445281 |
| N2AB | 20634 | 62125;62126;62127 | chr2:178580556;178580555;178580554 | chr2:179445283;179445282;179445281 |
| N2A | 19707 | 59344;59345;59346 | chr2:178580556;178580555;178580554 | chr2:179445283;179445282;179445281 |
| N2B | 13210 | 39853;39854;39855 | chr2:178580556;178580555;178580554 | chr2:179445283;179445282;179445281 |
| Novex-1 | 13335 | 40228;40229;40230 | chr2:178580556;178580555;178580554 | chr2:179445283;179445282;179445281 |
| Novex-2 | 13402 | 40429;40430;40431 | chr2:178580556;178580555;178580554 | chr2:179445283;179445282;179445281 |
| 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 | None | None | 1.0 | N | 0.763 | 0.502 | 0.32714864917 | gnomAD-4.0.0 | 1.20034E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31253E-06 | 0 | 0 |
| A/V | rs781002289  |
-0.233 | 1.0 | N | 0.638 | 0.369 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.12778E-04 | None | 0 | None | 0 | 8.96E-06 | 0 |
| A/V | rs781002289 |
-0.233 | 1.0 | N | 0.638 | 0.369 | None | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31251E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7483 | likely_pathogenic | 0.7733 | pathogenic | -0.759 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| A/D | 0.9284 | likely_pathogenic | 0.9343 | pathogenic | -0.734 | Destabilizing | 1.0 | D | 0.8 | deleterious | N | 0.505360524 | None | None | I |
| A/E | 0.8757 | likely_pathogenic | 0.8717 | pathogenic | -0.866 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| A/F | 0.9322 | likely_pathogenic | 0.9369 | pathogenic | -0.974 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| A/G | 0.4845 | ambiguous | 0.4356 | ambiguous | -0.652 | Destabilizing | 1.0 | D | 0.545 | neutral | N | 0.505614014 | None | None | I |
| A/H | 0.8759 | likely_pathogenic | 0.8864 | pathogenic | -0.696 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| A/I | 0.9264 | likely_pathogenic | 0.9247 | pathogenic | -0.428 | Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | I |
| A/K | 0.9336 | likely_pathogenic | 0.9322 | pathogenic | -0.958 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| A/L | 0.8804 | likely_pathogenic | 0.8732 | pathogenic | -0.428 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| A/M | 0.8555 | likely_pathogenic | 0.8405 | pathogenic | -0.392 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | I |
| A/N | 0.775 | likely_pathogenic | 0.7645 | pathogenic | -0.566 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | I |
| A/P | 0.9264 | likely_pathogenic | 0.941 | pathogenic | -0.428 | Destabilizing | 1.0 | D | 0.763 | deleterious | N | 0.474886006 | None | None | I |
| A/Q | 0.7982 | likely_pathogenic | 0.7867 | pathogenic | -0.849 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | I |
| A/R | 0.8703 | likely_pathogenic | 0.8806 | pathogenic | -0.448 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| A/S | 0.1538 | likely_benign | 0.1435 | benign | -0.792 | Destabilizing | 1.0 | D | 0.553 | neutral | N | 0.461149844 | None | None | I |
| A/T | 0.6054 | likely_pathogenic | 0.5768 | pathogenic | -0.848 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | N | 0.492990261 | None | None | I |
| A/V | 0.6922 | likely_pathogenic | 0.7017 | pathogenic | -0.428 | Destabilizing | 1.0 | D | 0.638 | neutral | N | 0.49826574 | None | None | I |
| A/W | 0.9826 | likely_pathogenic | 0.9863 | pathogenic | -1.149 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | I |
| A/Y | 0.9348 | likely_pathogenic | 0.9389 | pathogenic | -0.811 | Destabilizing | 1.0 | D | 0.805 | 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.