Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32680 | 98263;98264;98265 | chr2:178540128;178540127;178540126 | chr2:179404855;179404854;179404853 |
| N2AB | 31039 | 93340;93341;93342 | chr2:178540128;178540127;178540126 | chr2:179404855;179404854;179404853 |
| N2A | 30112 | 90559;90560;90561 | chr2:178540128;178540127;178540126 | chr2:179404855;179404854;179404853 |
| N2B | 23615 | 71068;71069;71070 | chr2:178540128;178540127;178540126 | chr2:179404855;179404854;179404853 |
| Novex-1 | 23740 | 71443;71444;71445 | chr2:178540128;178540127;178540126 | chr2:179404855;179404854;179404853 |
| Novex-2 | 23807 | 71644;71645;71646 | chr2:178540128;178540127;178540126 | chr2:179404855;179404854;179404853 |
| 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/T | rs1340922711  |
0.035 | 0.999 | N | 0.664 | 0.332 | 0.28722502521 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| A/T | rs1340922711 |
0.035 | 0.999 | N | 0.664 | 0.332 | 0.28722502521 | gnomAD-4.0.0 | 3.19049E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86873E-06 | 1.43435E-05 | 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 | 0.6577 | likely_pathogenic | 0.7095 | pathogenic | -0.752 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| A/D | 0.5832 | likely_pathogenic | 0.7059 | pathogenic | -0.391 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.456470338 | None | None | N |
| A/E | 0.5067 | ambiguous | 0.637 | pathogenic | -0.547 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| A/F | 0.5686 | likely_pathogenic | 0.6641 | pathogenic | -0.873 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | N |
| A/G | 0.296 | likely_benign | 0.357 | ambiguous | -0.142 | Destabilizing | 0.999 | D | 0.535 | neutral | N | 0.493348284 | None | None | N |
| A/H | 0.702 | likely_pathogenic | 0.7727 | pathogenic | -0.157 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| A/I | 0.3354 | likely_benign | 0.4191 | ambiguous | -0.347 | Destabilizing | 0.998 | D | 0.618 | neutral | None | None | None | None | N |
| A/K | 0.6696 | likely_pathogenic | 0.7754 | pathogenic | -0.336 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| A/L | 0.2813 | likely_benign | 0.3419 | ambiguous | -0.347 | Destabilizing | 0.504 | D | 0.449 | neutral | None | None | None | None | N |
| A/M | 0.3234 | likely_benign | 0.4024 | ambiguous | -0.385 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| A/N | 0.4916 | ambiguous | 0.5843 | pathogenic | -0.1 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| A/P | 0.5474 | ambiguous | 0.6728 | pathogenic | -0.254 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.509035386 | None | None | N |
| A/Q | 0.5354 | ambiguous | 0.6136 | pathogenic | -0.375 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| A/R | 0.6018 | likely_pathogenic | 0.6936 | pathogenic | 0.078 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| A/S | 0.1422 | likely_benign | 0.1672 | benign | -0.282 | Destabilizing | 0.999 | D | 0.522 | neutral | N | 0.42306984 | None | None | N |
| A/T | 0.1465 | likely_benign | 0.1907 | benign | -0.364 | Destabilizing | 0.999 | D | 0.664 | neutral | N | 0.50362678 | None | None | N |
| A/V | 0.1762 | likely_benign | 0.2331 | benign | -0.254 | Destabilizing | 0.992 | D | 0.487 | neutral | N | 0.5068218 | None | None | N |
| A/W | 0.8958 | likely_pathogenic | 0.9284 | pathogenic | -0.971 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| A/Y | 0.7131 | likely_pathogenic | 0.7834 | pathogenic | -0.631 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
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.