Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27871 | 83836;83837;83838 | chr2:178562521;178562520;178562519 | chr2:179427248;179427247;179427246 |
| N2AB | 26230 | 78913;78914;78915 | chr2:178562521;178562520;178562519 | chr2:179427248;179427247;179427246 |
| N2A | 25303 | 76132;76133;76134 | chr2:178562521;178562520;178562519 | chr2:179427248;179427247;179427246 |
| N2B | 18806 | 56641;56642;56643 | chr2:178562521;178562520;178562519 | chr2:179427248;179427247;179427246 |
| Novex-1 | 18931 | 57016;57017;57018 | chr2:178562521;178562520;178562519 | chr2:179427248;179427247;179427246 |
| Novex-2 | 18998 | 57217;57218;57219 | chr2:178562521;178562520;178562519 | chr2:179427248;179427247;179427246 |
| 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 | rs746421338  |
0.353 | 0.01 | N | 0.305 | 0.179 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 2.87853E-04 | 0 | 0 |
| T/I | rs746421338 |
0.353 | 0.01 | N | 0.305 | 0.179 | None | gnomAD-4.0.0 | 6.16812E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.75488E-05 | 3.48068E-04 | 4.49987E-06 | 0 | 0 |
| T/N | None | None | 0.716 | N | 0.453 | 0.187 | 0.351180957027 | gnomAD-4.0.0 | 6.85346E-07 | None | None | None | None | N | None | 3.00282E-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 | 0.1164 | likely_benign | 0.1255 | benign | -0.603 | Destabilizing | 0.046 | N | 0.389 | neutral | N | 0.47085226 | None | None | N |
| T/C | 0.4877 | ambiguous | 0.5166 | ambiguous | -0.451 | Destabilizing | 0.996 | D | 0.505 | neutral | None | None | None | None | N |
| T/D | 0.5193 | ambiguous | 0.5721 | pathogenic | -0.01 | Destabilizing | 0.488 | N | 0.521 | neutral | None | None | None | None | N |
| T/E | 0.4489 | ambiguous | 0.5012 | ambiguous | 0.065 | Stabilizing | 0.76 | D | 0.495 | neutral | None | None | None | None | N |
| T/F | 0.2584 | likely_benign | 0.2834 | benign | -0.533 | Destabilizing | 0.977 | D | 0.605 | neutral | None | None | None | None | N |
| T/G | 0.3241 | likely_benign | 0.3518 | ambiguous | -0.913 | Destabilizing | 0.888 | D | 0.56 | neutral | None | None | None | None | N |
| T/H | 0.3308 | likely_benign | 0.3745 | ambiguous | -1.085 | Destabilizing | 0.997 | D | 0.577 | neutral | None | None | None | None | N |
| T/I | 0.1845 | likely_benign | 0.1903 | benign | 0.148 | Stabilizing | 0.01 | N | 0.305 | neutral | N | 0.520772532 | None | None | N |
| T/K | 0.3902 | ambiguous | 0.4354 | ambiguous | -0.446 | Destabilizing | 0.816 | D | 0.495 | neutral | None | None | None | None | N |
| T/L | 0.1205 | likely_benign | 0.1295 | benign | 0.148 | Stabilizing | 0.478 | N | 0.459 | neutral | None | None | None | None | N |
| T/M | 0.0969 | likely_benign | 0.1029 | benign | 0.031 | Stabilizing | 0.94 | D | 0.535 | neutral | None | None | None | None | N |
| T/N | 0.1502 | likely_benign | 0.1717 | benign | -0.665 | Destabilizing | 0.716 | D | 0.453 | neutral | N | 0.472991854 | None | None | N |
| T/P | 0.6039 | likely_pathogenic | 0.6606 | pathogenic | -0.069 | Destabilizing | 0.836 | D | 0.541 | neutral | N | 0.499769842 | None | None | N |
| T/Q | 0.3198 | likely_benign | 0.353 | ambiguous | -0.612 | Destabilizing | 0.937 | D | 0.536 | neutral | None | None | None | None | N |
| T/R | 0.3402 | ambiguous | 0.3945 | ambiguous | -0.416 | Destabilizing | 0.988 | D | 0.54 | neutral | None | None | None | None | N |
| T/S | 0.1219 | likely_benign | 0.1342 | benign | -0.934 | Destabilizing | 0.009 | N | 0.201 | neutral | N | 0.475362743 | None | None | N |
| T/V | 0.1598 | likely_benign | 0.1592 | benign | -0.069 | Destabilizing | 0.041 | N | 0.163 | neutral | None | None | None | None | N |
| T/W | 0.6669 | likely_pathogenic | 0.7074 | pathogenic | -0.599 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | N |
| T/Y | 0.3329 | likely_benign | 0.365 | ambiguous | -0.274 | Destabilizing | 0.996 | D | 0.614 | 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.