Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29362 | 88309;88310;88311 | chr2:178557070;178557069;178557068 | chr2:179421797;179421796;179421795 |
| N2AB | 27721 | 83386;83387;83388 | chr2:178557070;178557069;178557068 | chr2:179421797;179421796;179421795 |
| N2A | 26794 | 80605;80606;80607 | chr2:178557070;178557069;178557068 | chr2:179421797;179421796;179421795 |
| N2B | 20297 | 61114;61115;61116 | chr2:178557070;178557069;178557068 | chr2:179421797;179421796;179421795 |
| Novex-1 | 20422 | 61489;61490;61491 | chr2:178557070;178557069;178557068 | chr2:179421797;179421796;179421795 |
| Novex-2 | 20489 | 61690;61691;61692 | chr2:178557070;178557069;178557068 | chr2:179421797;179421796;179421795 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs1414215784  |
-0.885 | 0.989 | D | 0.651 | 0.53 | 0.44153150616 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| D/G | rs1414215784 |
-0.885 | 0.989 | D | 0.651 | 0.53 | 0.44153150616 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| D/G | rs1414215784 |
-0.885 | 0.989 | D | 0.651 | 0.53 | 0.44153150616 | gnomAD-4.0.0 | 8.67641E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.10187E-05 | 0 | 1.60123E-05 |
| D/N | rs546300309 |
-0.442 | 1.0 | N | 0.722 | 0.366 | 0.383921772103 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| D/N | rs546300309 |
-0.442 | 1.0 | N | 0.722 | 0.366 | 0.383921772103 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 1.20674E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs546300309 |
-0.442 | 1.0 | N | 0.722 | 0.366 | 0.383921772103 | gnomAD-4.0.0 | 1.85918E-05 | None | None | None | None | I | None | 1.19949E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 1.61048E-05 | 1.09839E-05 | 1.60067E-05 |
| D/Y | rs546300309 |
-0.54 | 0.438 | D | 0.558 | 0.361 | 0.626687164261 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/Y | rs546300309 |
-0.54 | 0.438 | D | 0.558 | 0.361 | 0.626687164261 | gnomAD-4.0.0 | 6.84296E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15966E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7047 | likely_pathogenic | 0.5362 | ambiguous | -0.733 | Destabilizing | 0.993 | D | 0.669 | neutral | N | 0.50013501 | None | None | I |
| D/C | 0.931 | likely_pathogenic | 0.8701 | pathogenic | -0.238 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | I |
| D/E | 0.6587 | likely_pathogenic | 0.5244 | ambiguous | -0.702 | Destabilizing | 0.989 | D | 0.464 | neutral | N | 0.499121052 | None | None | I |
| D/F | 0.9613 | likely_pathogenic | 0.9233 | pathogenic | -0.528 | Destabilizing | 0.99 | D | 0.715 | prob.delet. | None | None | None | None | I |
| D/G | 0.713 | likely_pathogenic | 0.5624 | ambiguous | -1.066 | Destabilizing | 0.989 | D | 0.651 | neutral | D | 0.525026894 | None | None | I |
| D/H | 0.7957 | likely_pathogenic | 0.693 | pathogenic | -0.875 | Destabilizing | 0.999 | D | 0.745 | deleterious | N | 0.520151822 | None | None | I |
| D/I | 0.9097 | likely_pathogenic | 0.8207 | pathogenic | 0.146 | Stabilizing | 0.995 | D | 0.739 | prob.delet. | None | None | None | None | I |
| D/K | 0.9223 | likely_pathogenic | 0.8733 | pathogenic | -0.338 | Destabilizing | 0.998 | D | 0.744 | deleterious | None | None | None | None | I |
| D/L | 0.8801 | likely_pathogenic | 0.7889 | pathogenic | 0.146 | Stabilizing | 0.99 | D | 0.701 | prob.neutral | None | None | None | None | I |
| D/M | 0.9619 | likely_pathogenic | 0.9214 | pathogenic | 0.691 | Stabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | I |
| D/N | 0.2393 | likely_benign | 0.156 | benign | -0.757 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | N | 0.487057184 | None | None | I |
| D/P | 0.9311 | likely_pathogenic | 0.8865 | pathogenic | -0.123 | Destabilizing | 0.999 | D | 0.759 | deleterious | None | None | None | None | I |
| D/Q | 0.8599 | likely_pathogenic | 0.7797 | pathogenic | -0.637 | Destabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | I |
| D/R | 0.9062 | likely_pathogenic | 0.8531 | pathogenic | -0.285 | Destabilizing | 0.998 | D | 0.77 | deleterious | None | None | None | None | I |
| D/S | 0.3698 | ambiguous | 0.2356 | benign | -1.023 | Destabilizing | 0.998 | D | 0.717 | prob.delet. | None | None | None | None | I |
| D/T | 0.5704 | likely_pathogenic | 0.4011 | ambiguous | -0.739 | Destabilizing | 0.998 | D | 0.741 | deleterious | None | None | None | None | I |
| D/V | 0.7951 | likely_pathogenic | 0.6592 | pathogenic | -0.123 | Destabilizing | 0.993 | D | 0.709 | prob.delet. | D | 0.523759446 | None | None | I |
| D/W | 0.9895 | likely_pathogenic | 0.9805 | pathogenic | -0.361 | Destabilizing | 0.999 | D | 0.718 | prob.delet. | None | None | None | None | I |
| D/Y | 0.7896 | likely_pathogenic | 0.6796 | pathogenic | -0.282 | Destabilizing | 0.438 | N | 0.558 | neutral | D | 0.557120801 | None | None | I |
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.