Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16463 | 49612;49613;49614 | chr2:178613896;178613895;178613894 | chr2:179478623;179478622;179478621 |
| N2AB | 14822 | 44689;44690;44691 | chr2:178613896;178613895;178613894 | chr2:179478623;179478622;179478621 |
| N2A | 13895 | 41908;41909;41910 | chr2:178613896;178613895;178613894 | chr2:179478623;179478622;179478621 |
| N2B | 7398 | 22417;22418;22419 | chr2:178613896;178613895;178613894 | chr2:179478623;179478622;179478621 |
| Novex-1 | 7523 | 22792;22793;22794 | chr2:178613896;178613895;178613894 | chr2:179478623;179478622;179478621 |
| Novex-2 | 7590 | 22993;22994;22995 | chr2:178613896;178613895;178613894 | chr2:179478623;179478622;179478621 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs541307234  |
None | 0.994 | D | 0.409 | 0.49 | 0.584859779323 | gnomAD-4.0.0 | 6.85616E-07 | None | None | None | None | N | None | 3.0003E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/N | None | -1.133 | 0.998 | N | 0.405 | 0.362 | 0.396794106654 | gnomAD-2.1.1 | 1.63E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.12145E-04 | None | 6.7E-05 | None | 0 | 0 | 0 |
| T/N | None | -1.133 | 0.998 | N | 0.405 | 0.362 | 0.396794106654 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.95389E-04 | None | 0 | 0 | 0 | 0 | 0 |
| T/N | None | -1.133 | 0.998 | N | 0.405 | 0.362 | 0.396794106654 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| T/N | None | -1.133 | 0.998 | N | 0.405 | 0.362 | 0.396794106654 | gnomAD-4.0.0 | 6.82967E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.47407E-05 | None | 0 | 0 | 1.69743E-06 | 6.63101E-05 | 1.60406E-05 |
| T/S | rs541307234 |
-1.327 | 0.835 | N | 0.501 | 0.152 | 0.18995819373 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 6.49E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/S | rs541307234 |
-1.327 | 0.835 | N | 0.501 | 0.152 | 0.18995819373 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | rs541307234 |
-1.327 | 0.835 | N | 0.501 | 0.152 | 0.18995819373 | gnomAD-4.0.0 | 6.58068E-06 | None | None | None | None | N | None | 2.41406E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.2014 | likely_benign | 0.1654 | benign | -0.785 | Destabilizing | 0.122 | N | 0.146 | neutral | N | 0.491029112 | None | None | N |
| T/C | 0.6097 | likely_pathogenic | 0.5476 | ambiguous | -0.631 | Destabilizing | 1.0 | D | 0.447 | neutral | None | None | None | None | N |
| T/D | 0.8141 | likely_pathogenic | 0.8077 | pathogenic | -0.98 | Destabilizing | 0.996 | D | 0.411 | neutral | None | None | None | None | N |
| T/E | 0.7876 | likely_pathogenic | 0.7982 | pathogenic | -0.932 | Destabilizing | 0.985 | D | 0.412 | neutral | None | None | None | None | N |
| T/F | 0.6992 | likely_pathogenic | 0.6537 | pathogenic | -0.699 | Destabilizing | 0.999 | D | 0.527 | neutral | None | None | None | None | N |
| T/G | 0.3635 | ambiguous | 0.2568 | benign | -1.096 | Destabilizing | 0.942 | D | 0.454 | neutral | None | None | None | None | N |
| T/H | 0.6172 | likely_pathogenic | 0.5875 | pathogenic | -1.393 | Destabilizing | 1.0 | D | 0.515 | neutral | None | None | None | None | N |
| T/I | 0.7132 | likely_pathogenic | 0.7214 | pathogenic | -0.033 | Destabilizing | 0.994 | D | 0.409 | neutral | D | 0.623560331 | None | None | N |
| T/K | 0.6381 | likely_pathogenic | 0.6722 | pathogenic | -0.857 | Destabilizing | 0.97 | D | 0.419 | neutral | None | None | None | None | N |
| T/L | 0.321 | likely_benign | 0.2995 | benign | -0.033 | Destabilizing | 0.97 | D | 0.425 | neutral | None | None | None | None | N |
| T/M | 0.2464 | likely_benign | 0.2424 | benign | 0.256 | Stabilizing | 1.0 | D | 0.446 | neutral | None | None | None | None | N |
| T/N | 0.3017 | likely_benign | 0.3031 | benign | -1.035 | Destabilizing | 0.998 | D | 0.405 | neutral | N | 0.484742981 | None | None | N |
| T/P | 0.8327 | likely_pathogenic | 0.8332 | pathogenic | -0.25 | Destabilizing | 0.994 | D | 0.413 | neutral | D | 0.639326629 | None | None | N |
| T/Q | 0.509 | ambiguous | 0.4948 | ambiguous | -1.155 | Destabilizing | 0.999 | D | 0.446 | neutral | None | None | None | None | N |
| T/R | 0.5538 | ambiguous | 0.5948 | pathogenic | -0.661 | Destabilizing | 0.996 | D | 0.435 | neutral | None | None | None | None | N |
| T/S | 0.1765 | likely_benign | 0.134 | benign | -1.221 | Destabilizing | 0.835 | D | 0.501 | neutral | N | 0.474469379 | None | None | N |
| T/V | 0.4777 | ambiguous | 0.4616 | ambiguous | -0.25 | Destabilizing | 0.97 | D | 0.435 | neutral | None | None | None | None | N |
| T/W | 0.9292 | likely_pathogenic | 0.9203 | pathogenic | -0.703 | Destabilizing | 1.0 | D | 0.57 | neutral | None | None | None | None | N |
| T/Y | 0.7418 | likely_pathogenic | 0.7194 | pathogenic | -0.432 | Destabilizing | 0.999 | D | 0.531 | neutral | 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.