Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23868 | 71827;71828;71829 | chr2:178574530;178574529;178574528 | chr2:179439257;179439256;179439255 |
| N2AB | 22227 | 66904;66905;66906 | chr2:178574530;178574529;178574528 | chr2:179439257;179439256;179439255 |
| N2A | 21300 | 64123;64124;64125 | chr2:178574530;178574529;178574528 | chr2:179439257;179439256;179439255 |
| N2B | 14803 | 44632;44633;44634 | chr2:178574530;178574529;178574528 | chr2:179439257;179439256;179439255 |
| Novex-1 | 14928 | 45007;45008;45009 | chr2:178574530;178574529;178574528 | chr2:179439257;179439256;179439255 |
| Novex-2 | 14995 | 45208;45209;45210 | chr2:178574530;178574529;178574528 | chr2:179439257;179439256;179439255 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs763316990  |
0.084 | 0.98 | N | 0.556 | 0.151 | 0.245101548738 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| R/Q | rs763316990 |
0.084 | 0.98 | N | 0.556 | 0.151 | 0.245101548738 | gnomAD-4.0.0 | 7.52714E-06 | None | None | None | None | N | None | 0 | 0 | None | 3.8276E-05 | 2.52067E-05 | None | 1.87266E-05 | 0 | 5.39745E-06 | 2.31895E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7154 | likely_pathogenic | 0.6581 | pathogenic | -0.301 | Destabilizing | 0.825 | D | 0.529 | neutral | None | None | None | None | N |
| R/C | 0.3242 | likely_benign | 0.2974 | benign | -0.239 | Destabilizing | 0.999 | D | 0.686 | prob.neutral | None | None | None | None | N |
| R/D | 0.9227 | likely_pathogenic | 0.9121 | pathogenic | -0.069 | Destabilizing | 0.976 | D | 0.606 | neutral | None | None | None | None | N |
| R/E | 0.6636 | likely_pathogenic | 0.6324 | pathogenic | 0.005 | Stabilizing | 0.851 | D | 0.463 | neutral | None | None | None | None | N |
| R/F | 0.8501 | likely_pathogenic | 0.8232 | pathogenic | -0.44 | Destabilizing | 0.996 | D | 0.665 | neutral | None | None | None | None | N |
| R/G | 0.5587 | ambiguous | 0.5098 | ambiguous | -0.537 | Destabilizing | 0.956 | D | 0.615 | neutral | N | 0.485849095 | None | None | N |
| R/H | 0.2412 | likely_benign | 0.2184 | benign | -1.004 | Destabilizing | 0.996 | D | 0.507 | neutral | None | None | None | None | N |
| R/I | 0.4786 | ambiguous | 0.443 | ambiguous | 0.298 | Stabilizing | 0.988 | D | 0.666 | neutral | None | None | None | None | N |
| R/K | 0.1391 | likely_benign | 0.1217 | benign | -0.314 | Destabilizing | 0.015 | N | 0.155 | neutral | None | None | None | None | N |
| R/L | 0.4902 | ambiguous | 0.4669 | ambiguous | 0.298 | Stabilizing | 0.956 | D | 0.615 | neutral | N | 0.48130728 | None | None | N |
| R/M | 0.5005 | ambiguous | 0.4689 | ambiguous | 0.025 | Stabilizing | 0.999 | D | 0.581 | neutral | None | None | None | None | N |
| R/N | 0.8484 | likely_pathogenic | 0.8212 | pathogenic | 0.146 | Stabilizing | 0.919 | D | 0.522 | neutral | None | None | None | None | N |
| R/P | 0.8492 | likely_pathogenic | 0.8109 | pathogenic | 0.119 | Stabilizing | 0.994 | D | 0.652 | neutral | N | 0.478133689 | None | None | N |
| R/Q | 0.1604 | likely_benign | 0.1478 | benign | -0.054 | Destabilizing | 0.98 | D | 0.556 | neutral | N | 0.493063069 | None | None | N |
| R/S | 0.8229 | likely_pathogenic | 0.7898 | pathogenic | -0.389 | Destabilizing | 0.919 | D | 0.559 | neutral | None | None | None | None | N |
| R/T | 0.5976 | likely_pathogenic | 0.5486 | ambiguous | -0.167 | Destabilizing | 0.919 | D | 0.59 | neutral | None | None | None | None | N |
| R/V | 0.592 | likely_pathogenic | 0.5518 | ambiguous | 0.119 | Stabilizing | 0.988 | D | 0.619 | neutral | None | None | None | None | N |
| R/W | 0.378 | ambiguous | 0.3607 | ambiguous | -0.329 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | None | None | None | None | N |
| R/Y | 0.6646 | likely_pathogenic | 0.6274 | pathogenic | 0.044 | Stabilizing | 0.996 | D | 0.662 | 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.