Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22320 | 67183;67184;67185 | chr2:178580421;178580420;178580419 | chr2:179445148;179445147;179445146 |
| N2AB | 20679 | 62260;62261;62262 | chr2:178580421;178580420;178580419 | chr2:179445148;179445147;179445146 |
| N2A | 19752 | 59479;59480;59481 | chr2:178580421;178580420;178580419 | chr2:179445148;179445147;179445146 |
| N2B | 13255 | 39988;39989;39990 | chr2:178580421;178580420;178580419 | chr2:179445148;179445147;179445146 |
| Novex-1 | 13380 | 40363;40364;40365 | chr2:178580421;178580420;178580419 | chr2:179445148;179445147;179445146 |
| Novex-2 | 13447 | 40564;40565;40566 | chr2:178580421;178580420;178580419 | chr2:179445148;179445147;179445146 |
| 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/C | rs772361876  |
-1.329 | 0.998 | N | 0.475 | 0.508 | 0.686686103294 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 8.91E-06 | 0 |
| R/C | rs772361876 |
-1.329 | 0.998 | N | 0.475 | 0.508 | 0.686686103294 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94326E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs772361876 |
-1.329 | 0.998 | N | 0.475 | 0.508 | 0.686686103294 | gnomAD-4.0.0 | 1.92173E-05 | None | None | None | None | N | None | 4.00149E-05 | 1.66706E-05 | None | 0 | 2.23604E-05 | None | 0 | 0 | 1.44136E-05 | 8.78677E-05 | 1.60133E-05 |
| R/H | rs771424865 |
-1.876 | 0.017 | N | 0.325 | 0.317 | None | gnomAD-2.1.1 | 3.93E-05 | None | None | None | None | N | None | 4.13E-05 | 8.49E-05 | None | 0 | 5.16E-05 | None | 0 | None | 4E-05 | 3.92E-05 | 0 |
| R/H | rs771424865 |
-1.876 | 0.017 | N | 0.325 | 0.317 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 7.24E-05 | 2.6202E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/H | rs771424865 |
-1.876 | 0.017 | N | 0.325 | 0.317 | None | gnomAD-4.0.0 | 2.72773E-05 | None | None | None | None | N | None | 9.35054E-05 | 1.16713E-04 | None | 0 | 2.23524E-05 | None | 1.56314E-05 | 1.64636E-04 | 2.2892E-05 | 0 | 0 |
| R/L | None | None | 0.336 | N | 0.433 | 0.391 | 0.474798811001 | gnomAD-4.0.0 | 1.3689E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79941E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6579 | likely_pathogenic | 0.6511 | pathogenic | -1.487 | Destabilizing | 0.209 | N | 0.415 | neutral | None | None | None | None | N |
| R/C | 0.2236 | likely_benign | 0.2402 | benign | -1.508 | Destabilizing | 0.998 | D | 0.475 | neutral | N | 0.486500535 | None | None | N |
| R/D | 0.8951 | likely_pathogenic | 0.8914 | pathogenic | -0.435 | Destabilizing | 0.561 | D | 0.496 | neutral | None | None | None | None | N |
| R/E | 0.6083 | likely_pathogenic | 0.6011 | pathogenic | -0.256 | Destabilizing | 0.345 | N | 0.391 | neutral | None | None | None | None | N |
| R/F | 0.5941 | likely_pathogenic | 0.5909 | pathogenic | -1.001 | Destabilizing | 0.39 | N | 0.519 | neutral | None | None | None | None | N |
| R/G | 0.6117 | likely_pathogenic | 0.6247 | pathogenic | -1.847 | Destabilizing | 0.336 | N | 0.48 | neutral | N | 0.504739579 | None | None | N |
| R/H | 0.1355 | likely_benign | 0.1389 | benign | -1.853 | Destabilizing | 0.017 | N | 0.325 | neutral | N | 0.48598046 | None | None | N |
| R/I | 0.2937 | likely_benign | 0.2765 | benign | -0.481 | Destabilizing | 0.39 | N | 0.488 | neutral | None | None | None | None | N |
| R/K | 0.1542 | likely_benign | 0.1682 | benign | -1.329 | Destabilizing | 0.345 | N | 0.424 | neutral | None | None | None | None | N |
| R/L | 0.3208 | likely_benign | 0.311 | benign | -0.481 | Destabilizing | 0.336 | N | 0.433 | neutral | N | 0.468682779 | None | None | N |
| R/M | 0.3983 | ambiguous | 0.3973 | ambiguous | -0.864 | Destabilizing | 0.047 | N | 0.305 | neutral | None | None | None | None | N |
| R/N | 0.7622 | likely_pathogenic | 0.7594 | pathogenic | -0.956 | Destabilizing | 0.561 | D | 0.386 | neutral | None | None | None | None | N |
| R/P | 0.9686 | likely_pathogenic | 0.9706 | pathogenic | -0.799 | Destabilizing | 0.946 | D | 0.532 | neutral | D | 0.534542411 | None | None | N |
| R/Q | 0.1571 | likely_benign | 0.1593 | benign | -1.009 | Destabilizing | 0.561 | D | 0.395 | neutral | None | None | None | None | N |
| R/S | 0.6752 | likely_pathogenic | 0.6735 | pathogenic | -1.892 | Destabilizing | 0.032 | N | 0.281 | neutral | N | 0.457273706 | None | None | N |
| R/T | 0.372 | ambiguous | 0.3676 | ambiguous | -1.499 | Destabilizing | 0.39 | N | 0.471 | neutral | None | None | None | None | N |
| R/V | 0.3892 | ambiguous | 0.3686 | ambiguous | -0.799 | Destabilizing | 0.209 | N | 0.491 | neutral | None | None | None | None | N |
| R/W | 0.2277 | likely_benign | 0.2273 | benign | -0.49 | Destabilizing | 0.972 | D | 0.477 | neutral | None | None | None | None | N |
| R/Y | 0.3934 | ambiguous | 0.3996 | ambiguous | -0.281 | Destabilizing | 0.017 | N | 0.377 | 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.