Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3150 | 9673;9674;9675 | chr2:178767782;178767781;178767780 | chr2:179632509;179632508;179632507 |
| N2AB | 3150 | 9673;9674;9675 | chr2:178767782;178767781;178767780 | chr2:179632509;179632508;179632507 |
| N2A | 3150 | 9673;9674;9675 | chr2:178767782;178767781;178767780 | chr2:179632509;179632508;179632507 |
| N2B | 3104 | 9535;9536;9537 | chr2:178767782;178767781;178767780 | chr2:179632509;179632508;179632507 |
| Novex-1 | 3104 | 9535;9536;9537 | chr2:178767782;178767781;178767780 | chr2:179632509;179632508;179632507 |
| Novex-2 | 3104 | 9535;9536;9537 | chr2:178767782;178767781;178767780 | chr2:179632509;179632508;179632507 |
| Novex-3 | 3150 | 9673;9674;9675 | chr2:178767782;178767781;178767780 | chr2:179632509;179632508;179632507 |
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/G | rs146572907  |
-0.492 | 0.911 | N | 0.305 | 0.432 | 0.574021187364 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 6.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/G | rs146572907 |
-0.492 | 0.911 | N | 0.305 | 0.432 | 0.574021187364 | gnomAD-4.0.0 | 6.84087E-07 | None | None | None | None | N | None | 2.98686E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/L | None | None | 0.837 | N | 0.301 | 0.399 | 0.550293681976 | gnomAD-4.0.0 | 6.84079E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99302E-07 | 0 | 0 |
| R/Q | rs141093658 |
0.151 | 0.958 | N | 0.331 | 0.258 | None | gnomAD-2.1.1 | 2.83E-05 | None | None | None | None | N | None | 4.01E-05 | 2.82E-05 | None | 9.66E-05 | 0 | None | 0 | None | 0 | 2.33E-05 | 2.77393E-04 |
| R/Q | rs141093658 |
0.151 | 0.958 | N | 0.331 | 0.258 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs141093658 |
0.151 | 0.958 | N | 0.331 | 0.258 | None | gnomAD-4.0.0 | 2.47831E-05 | None | None | None | None | N | None | 4.00384E-05 | 3.33311E-05 | None | 6.75539E-05 | 0 | None | 1.56265E-05 | 0 | 2.20338E-05 | 0 | 9.60215E-05 |
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 | 0.7074 | likely_pathogenic | 0.7687 | pathogenic | -0.219 | Destabilizing | 0.525 | D | 0.305 | neutral | None | None | None | None | N |
| R/C | 0.3867 | ambiguous | 0.4271 | ambiguous | -0.364 | Destabilizing | 0.998 | D | 0.255 | neutral | None | None | None | None | N |
| R/D | 0.9005 | likely_pathogenic | 0.9149 | pathogenic | 0.033 | Stabilizing | 0.728 | D | 0.313 | neutral | None | None | None | None | N |
| R/E | 0.6964 | likely_pathogenic | 0.7408 | pathogenic | 0.112 | Stabilizing | 0.029 | N | 0.116 | neutral | None | None | None | None | N |
| R/F | 0.7944 | likely_pathogenic | 0.8337 | pathogenic | -0.353 | Destabilizing | 0.974 | D | 0.277 | neutral | None | None | None | None | N |
| R/G | 0.6046 | likely_pathogenic | 0.6757 | pathogenic | -0.442 | Destabilizing | 0.911 | D | 0.305 | neutral | N | 0.502157437 | None | None | N |
| R/H | 0.1593 | likely_benign | 0.177 | benign | -0.818 | Destabilizing | 0.991 | D | 0.381 | neutral | None | None | None | None | N |
| R/I | 0.553 | ambiguous | 0.6115 | pathogenic | 0.345 | Stabilizing | 0.949 | D | 0.315 | neutral | None | None | None | None | N |
| R/K | 0.1964 | likely_benign | 0.219 | benign | -0.256 | Destabilizing | 0.007 | N | 0.102 | neutral | None | None | None | None | N |
| R/L | 0.5077 | ambiguous | 0.5596 | ambiguous | 0.345 | Stabilizing | 0.837 | D | 0.301 | neutral | N | 0.500444872 | None | None | N |
| R/M | 0.637 | likely_pathogenic | 0.7248 | pathogenic | -0.074 | Destabilizing | 0.991 | D | 0.334 | neutral | None | None | None | None | N |
| R/N | 0.7626 | likely_pathogenic | 0.8096 | pathogenic | 0.028 | Stabilizing | 0.842 | D | 0.313 | neutral | None | None | None | None | N |
| R/P | 0.9711 | likely_pathogenic | 0.9712 | pathogenic | 0.178 | Stabilizing | 0.986 | D | 0.328 | neutral | N | 0.502895438 | None | None | N |
| R/Q | 0.1807 | likely_benign | 0.2137 | benign | -0.099 | Destabilizing | 0.958 | D | 0.331 | neutral | N | 0.500273899 | None | None | N |
| R/S | 0.699 | likely_pathogenic | 0.7638 | pathogenic | -0.472 | Destabilizing | 0.525 | D | 0.303 | neutral | None | None | None | None | N |
| R/T | 0.4663 | ambiguous | 0.5519 | ambiguous | -0.244 | Destabilizing | 0.067 | N | 0.163 | neutral | None | None | None | None | N |
| R/V | 0.631 | likely_pathogenic | 0.6708 | pathogenic | 0.178 | Stabilizing | 0.728 | D | 0.332 | neutral | None | None | None | None | N |
| R/W | 0.3971 | ambiguous | 0.4555 | ambiguous | -0.289 | Destabilizing | 0.998 | D | 0.292 | neutral | None | None | None | None | N |
| R/Y | 0.6486 | likely_pathogenic | 0.6879 | pathogenic | 0.093 | Stabilizing | 0.991 | D | 0.284 | 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.