Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24011 | 72256;72257;72258 | chr2:178574101;178574100;178574099 | chr2:179438828;179438827;179438826 |
| N2AB | 22370 | 67333;67334;67335 | chr2:178574101;178574100;178574099 | chr2:179438828;179438827;179438826 |
| N2A | 21443 | 64552;64553;64554 | chr2:178574101;178574100;178574099 | chr2:179438828;179438827;179438826 |
| N2B | 14946 | 45061;45062;45063 | chr2:178574101;178574100;178574099 | chr2:179438828;179438827;179438826 |
| Novex-1 | 15071 | 45436;45437;45438 | chr2:178574101;178574100;178574099 | chr2:179438828;179438827;179438826 |
| Novex-2 | 15138 | 45637;45638;45639 | chr2:178574101;178574100;178574099 | chr2:179438828;179438827;179438826 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | rs746055019  |
-1.402 | 1.0 | N | 0.758 | 0.401 | None | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.54289E-04 | None | 0 | None | 0 | 1.57E-05 | 0 |
| P/S | rs746055019 |
-1.402 | 1.0 | N | 0.758 | 0.401 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93949E-04 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| P/S | rs746055019 |
-1.402 | 1.0 | N | 0.758 | 0.401 | None | gnomAD-4.0.0 | 7.4376E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.46269E-05 | None | 0 | 0 | 8.47719E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0898 | likely_benign | 0.0963 | benign | -1.421 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | N | 0.469049882 | None | None | N |
| P/C | 0.6836 | likely_pathogenic | 0.7211 | pathogenic | -0.81 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| P/D | 0.9275 | likely_pathogenic | 0.9379 | pathogenic | -1.198 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| P/E | 0.7616 | likely_pathogenic | 0.8026 | pathogenic | -1.244 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| P/F | 0.6739 | likely_pathogenic | 0.7177 | pathogenic | -1.224 | Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| P/G | 0.5389 | ambiguous | 0.5569 | ambiguous | -1.687 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| P/H | 0.52 | ambiguous | 0.5612 | ambiguous | -1.206 | Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| P/I | 0.62 | likely_pathogenic | 0.6481 | pathogenic | -0.809 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| P/K | 0.7848 | likely_pathogenic | 0.8357 | pathogenic | -1.17 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| P/L | 0.3252 | likely_benign | 0.3929 | ambiguous | -0.809 | Destabilizing | 1.0 | D | 0.825 | deleterious | D | 0.522210558 | None | None | N |
| P/M | 0.6569 | likely_pathogenic | 0.695 | pathogenic | -0.526 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| P/N | 0.8579 | likely_pathogenic | 0.8743 | pathogenic | -0.851 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| P/Q | 0.5127 | ambiguous | 0.5776 | pathogenic | -1.093 | Destabilizing | 1.0 | D | 0.799 | deleterious | D | 0.524238475 | None | None | N |
| P/R | 0.5939 | likely_pathogenic | 0.6852 | pathogenic | -0.568 | Destabilizing | 1.0 | D | 0.851 | deleterious | N | 0.503158479 | None | None | N |
| P/S | 0.2874 | likely_benign | 0.3151 | benign | -1.316 | Destabilizing | 1.0 | D | 0.758 | deleterious | N | 0.505284846 | None | None | N |
| P/T | 0.3797 | ambiguous | 0.4145 | ambiguous | -1.265 | Destabilizing | 1.0 | D | 0.76 | deleterious | D | 0.523731496 | None | None | N |
| P/V | 0.4429 | ambiguous | 0.4768 | ambiguous | -0.978 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| P/W | 0.8822 | likely_pathogenic | 0.9004 | pathogenic | -1.35 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| P/Y | 0.7014 | likely_pathogenic | 0.7281 | pathogenic | -1.096 | Destabilizing | 1.0 | D | 0.866 | deleterious | 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.