Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16653 | 50182;50183;50184 | chr2:178612568;178612567;178612566 | chr2:179477295;179477294;179477293 |
| N2AB | 15012 | 45259;45260;45261 | chr2:178612568;178612567;178612566 | chr2:179477295;179477294;179477293 |
| N2A | 14085 | 42478;42479;42480 | chr2:178612568;178612567;178612566 | chr2:179477295;179477294;179477293 |
| N2B | 7588 | 22987;22988;22989 | chr2:178612568;178612567;178612566 | chr2:179477295;179477294;179477293 |
| Novex-1 | 7713 | 23362;23363;23364 | chr2:178612568;178612567;178612566 | chr2:179477295;179477294;179477293 |
| Novex-2 | 7780 | 23563;23564;23565 | chr2:178612568;178612567;178612566 | chr2:179477295;179477294;179477293 |
| 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/L | rs746669146  |
0.305 | 0.989 | D | 0.764 | 0.567 | 0.689839040572 | gnomAD-2.1.1 | 8.44E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 7.07E-05 | None | 0 | 0 | 0 |
| S/L | rs746669146 |
0.305 | 0.989 | D | 0.764 | 0.567 | 0.689839040572 | gnomAD-4.0.0 | 4.82916E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.43262E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1776 | likely_benign | 0.1794 | benign | -0.538 | Destabilizing | 0.973 | D | 0.575 | neutral | D | 0.595897727 | None | None | N |
| S/C | 0.3623 | ambiguous | 0.3276 | benign | -0.606 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| S/D | 0.6838 | likely_pathogenic | 0.8172 | pathogenic | -1.385 | Destabilizing | 0.996 | D | 0.66 | neutral | None | None | None | None | N |
| S/E | 0.797 | likely_pathogenic | 0.8818 | pathogenic | -1.326 | Destabilizing | 0.996 | D | 0.663 | neutral | None | None | None | None | N |
| S/F | 0.5535 | ambiguous | 0.6154 | pathogenic | -0.54 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| S/G | 0.2138 | likely_benign | 0.1958 | benign | -0.839 | Destabilizing | 0.996 | D | 0.605 | neutral | None | None | None | None | N |
| S/H | 0.7098 | likely_pathogenic | 0.7811 | pathogenic | -1.405 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| S/I | 0.509 | ambiguous | 0.6074 | pathogenic | 0.171 | Stabilizing | 0.998 | D | 0.802 | deleterious | None | None | None | None | N |
| S/K | 0.9427 | likely_pathogenic | 0.9728 | pathogenic | -0.875 | Destabilizing | 0.996 | D | 0.659 | neutral | None | None | None | None | N |
| S/L | 0.2606 | likely_benign | 0.2669 | benign | 0.171 | Stabilizing | 0.989 | D | 0.764 | deleterious | D | 0.687849427 | None | None | N |
| S/M | 0.4722 | ambiguous | 0.4696 | ambiguous | 0.36 | Stabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| S/N | 0.3503 | ambiguous | 0.4077 | ambiguous | -1.147 | Destabilizing | 0.996 | D | 0.667 | neutral | None | None | None | None | N |
| S/P | 0.8574 | likely_pathogenic | 0.9258 | pathogenic | -0.03 | Destabilizing | 0.999 | D | 0.752 | deleterious | D | 0.682863541 | None | None | N |
| S/Q | 0.8049 | likely_pathogenic | 0.8566 | pathogenic | -1.207 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| S/R | 0.9239 | likely_pathogenic | 0.9662 | pathogenic | -0.872 | Destabilizing | 0.999 | D | 0.737 | prob.delet. | None | None | None | None | N |
| S/T | 0.1714 | likely_benign | 0.1829 | benign | -0.907 | Destabilizing | 0.543 | D | 0.415 | neutral | D | 0.551676934 | None | None | N |
| S/V | 0.4793 | ambiguous | 0.5594 | ambiguous | -0.03 | Destabilizing | 0.998 | D | 0.778 | deleterious | None | None | None | None | N |
| S/W | 0.7405 | likely_pathogenic | 0.8132 | pathogenic | -0.7 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| S/Y | 0.5303 | ambiguous | 0.629 | pathogenic | -0.353 | Destabilizing | 1.0 | D | 0.827 | 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.