Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27369 | 82330;82331;82332 | chr2:178564027;178564026;178564025 | chr2:179428754;179428753;179428752 |
| N2AB | 25728 | 77407;77408;77409 | chr2:178564027;178564026;178564025 | chr2:179428754;179428753;179428752 |
| N2A | 24801 | 74626;74627;74628 | chr2:178564027;178564026;178564025 | chr2:179428754;179428753;179428752 |
| N2B | 18304 | 55135;55136;55137 | chr2:178564027;178564026;178564025 | chr2:179428754;179428753;179428752 |
| Novex-1 | 18429 | 55510;55511;55512 | chr2:178564027;178564026;178564025 | chr2:179428754;179428753;179428752 |
| Novex-2 | 18496 | 55711;55712;55713 | chr2:178564027;178564026;178564025 | chr2:179428754;179428753;179428752 |
| 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/K | rs774715672  |
-0.447 | 0.022 | N | 0.263 | 0.088 | 0.139678290688 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 8.69E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| R/K | rs774715672 |
-0.447 | 0.022 | N | 0.263 | 0.088 | 0.139678290688 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 1.30993E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs774715672 |
-0.447 | 0.022 | N | 0.263 | 0.088 | 0.139678290688 | gnomAD-4.0.0 | 9.29575E-06 | None | None | None | None | I | None | 0 | 8.33472E-05 | None | 0 | 0 | None | 0 | 0 | 7.62875E-06 | 0 | 1.60118E-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 | 0.6912 | likely_pathogenic | 0.6732 | pathogenic | -0.308 | Destabilizing | 0.904 | D | 0.572 | neutral | None | None | None | None | I |
| R/C | 0.2025 | likely_benign | 0.219 | benign | -0.377 | Destabilizing | 0.999 | D | 0.862 | deleterious | None | None | None | None | I |
| R/D | 0.953 | likely_pathogenic | 0.9513 | pathogenic | -0.054 | Destabilizing | 0.971 | D | 0.773 | deleterious | None | None | None | None | I |
| R/E | 0.7049 | likely_pathogenic | 0.6956 | pathogenic | 0.015 | Stabilizing | 0.825 | D | 0.493 | neutral | None | None | None | None | I |
| R/F | 0.7907 | likely_pathogenic | 0.7842 | pathogenic | -0.459 | Destabilizing | 0.995 | D | 0.824 | deleterious | None | None | None | None | I |
| R/G | 0.6375 | likely_pathogenic | 0.6458 | pathogenic | -0.526 | Destabilizing | 0.877 | D | 0.539 | neutral | N | 0.495699286 | None | None | I |
| R/H | 0.1956 | likely_benign | 0.2031 | benign | -0.877 | Destabilizing | 0.995 | D | 0.626 | neutral | None | None | None | None | I |
| R/I | 0.3514 | ambiguous | 0.3157 | benign | 0.241 | Stabilizing | 0.985 | D | 0.847 | deleterious | None | None | None | None | I |
| R/K | 0.1241 | likely_benign | 0.1255 | benign | -0.352 | Destabilizing | 0.022 | N | 0.263 | neutral | N | 0.424384057 | None | None | I |
| R/L | 0.45 | ambiguous | 0.4372 | ambiguous | 0.241 | Stabilizing | 0.904 | D | 0.539 | neutral | None | None | None | None | I |
| R/M | 0.4782 | ambiguous | 0.4532 | ambiguous | -0.076 | Destabilizing | 0.998 | D | 0.601 | neutral | N | 0.48459647 | None | None | I |
| R/N | 0.8628 | likely_pathogenic | 0.8569 | pathogenic | 0.042 | Stabilizing | 0.971 | D | 0.62 | neutral | None | None | None | None | I |
| R/P | 0.8949 | likely_pathogenic | 0.9045 | pathogenic | 0.079 | Stabilizing | 0.985 | D | 0.859 | deleterious | None | None | None | None | I |
| R/Q | 0.1596 | likely_benign | 0.1642 | benign | -0.15 | Destabilizing | 0.971 | D | 0.652 | prob.neutral | None | None | None | None | I |
| R/S | 0.7656 | likely_pathogenic | 0.7567 | pathogenic | -0.492 | Destabilizing | 0.877 | D | 0.7 | prob.delet. | N | 0.468694261 | None | None | I |
| R/T | 0.4493 | ambiguous | 0.407 | ambiguous | -0.281 | Destabilizing | 0.961 | D | 0.573 | neutral | N | 0.481970923 | None | None | I |
| R/V | 0.4588 | ambiguous | 0.4193 | ambiguous | 0.079 | Stabilizing | 0.985 | D | 0.821 | deleterious | None | None | None | None | I |
| R/W | 0.4307 | ambiguous | 0.4444 | ambiguous | -0.356 | Destabilizing | 0.998 | D | 0.876 | deleterious | N | 0.496206265 | None | None | I |
| R/Y | 0.6502 | likely_pathogenic | 0.6716 | pathogenic | 0.012 | Stabilizing | 0.995 | D | 0.848 | deleterious | None | None | 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.