Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28542 | 85849;85850;85851 | chr2:178560508;178560507;178560506 | chr2:179425235;179425234;179425233 |
| N2AB | 26901 | 80926;80927;80928 | chr2:178560508;178560507;178560506 | chr2:179425235;179425234;179425233 |
| N2A | 25974 | 78145;78146;78147 | chr2:178560508;178560507;178560506 | chr2:179425235;179425234;179425233 |
| N2B | 19477 | 58654;58655;58656 | chr2:178560508;178560507;178560506 | chr2:179425235;179425234;179425233 |
| Novex-1 | 19602 | 59029;59030;59031 | chr2:178560508;178560507;178560506 | chr2:179425235;179425234;179425233 |
| Novex-2 | 19669 | 59230;59231;59232 | chr2:178560508;178560507;178560506 | chr2:179425235;179425234;179425233 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs554841820  |
-0.662 | 0.001 | N | 0.351 | 0.054 | 0.435590266561 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.1217E-04 | None | 0 | None | 0 | 0 | 0 |
| I/L | rs554841820 |
-0.662 | 0.001 | N | 0.351 | 0.054 | 0.435590266561 | gnomAD-4.0.0 | 2.73811E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.01056E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs554841820 |
-1.106 | None | N | 0.125 | 0.056 | 0.229264304666 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 5.82E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| I/V | rs554841820 |
-1.106 | None | N | 0.125 | 0.056 | 0.229264304666 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 3.27869E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs554841820 |
-1.106 | None | N | 0.125 | 0.056 | 0.229264304666 | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 2.9E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/V | rs554841820 |
-1.106 | None | N | 0.125 | 0.056 | 0.229264304666 | gnomAD-4.0.0 | 1.11587E-05 | None | None | None | None | N | None | 0 | 2.3352E-04 | None | 0 | 8.93775E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2042 | likely_benign | 0.1685 | benign | -1.925 | Destabilizing | None | N | 0.289 | neutral | None | None | None | None | N |
| I/C | 0.495 | ambiguous | 0.4348 | ambiguous | -1.228 | Destabilizing | 0.204 | N | 0.434 | neutral | None | None | None | None | N |
| I/D | 0.6215 | likely_pathogenic | 0.5395 | ambiguous | -1.481 | Destabilizing | 0.018 | N | 0.453 | neutral | None | None | None | None | N |
| I/E | 0.3598 | ambiguous | 0.3017 | benign | -1.328 | Destabilizing | None | N | 0.45 | neutral | None | None | None | None | N |
| I/F | 0.1384 | likely_benign | 0.1248 | benign | -1.06 | Destabilizing | 0.035 | N | 0.457 | neutral | None | None | None | None | N |
| I/G | 0.4673 | ambiguous | 0.3886 | ambiguous | -2.379 | Highly Destabilizing | 0.007 | N | 0.317 | neutral | None | None | None | None | N |
| I/H | 0.4779 | ambiguous | 0.3922 | ambiguous | -1.423 | Destabilizing | 0.439 | N | 0.601 | neutral | None | None | None | None | N |
| I/K | 0.2457 | likely_benign | 0.1914 | benign | -1.369 | Destabilizing | 0.011 | N | 0.403 | neutral | N | 0.486836012 | None | None | N |
| I/L | 0.1202 | likely_benign | 0.1025 | benign | -0.669 | Destabilizing | 0.001 | N | 0.351 | neutral | N | 0.473223728 | None | None | N |
| I/M | 0.0827 | likely_benign | 0.076 | benign | -0.618 | Destabilizing | 0.087 | N | 0.429 | neutral | N | 0.50071976 | None | None | N |
| I/N | 0.2619 | likely_benign | 0.2224 | benign | -1.557 | Destabilizing | 0.035 | N | 0.603 | neutral | None | None | None | None | N |
| I/P | 0.8808 | likely_pathogenic | 0.8484 | pathogenic | -1.062 | Destabilizing | 0.068 | N | 0.604 | neutral | None | None | None | None | N |
| I/Q | 0.2788 | likely_benign | 0.2237 | benign | -1.509 | Destabilizing | 0.035 | N | 0.637 | neutral | None | None | None | None | N |
| I/R | 0.2129 | likely_benign | 0.159 | benign | -0.97 | Destabilizing | 0.026 | N | 0.629 | neutral | N | 0.487089502 | None | None | N |
| I/S | 0.2334 | likely_benign | 0.1969 | benign | -2.277 | Highly Destabilizing | 0.007 | N | 0.377 | neutral | None | None | None | None | N |
| I/T | 0.1401 | likely_benign | 0.1173 | benign | -1.977 | Destabilizing | None | N | 0.276 | neutral | N | 0.487539819 | None | None | N |
| I/V | 0.0512 | likely_benign | 0.0505 | benign | -1.062 | Destabilizing | None | N | 0.125 | neutral | N | 0.371731369 | None | None | N |
| I/W | 0.7549 | likely_pathogenic | 0.66 | pathogenic | -1.244 | Destabilizing | 0.747 | D | 0.663 | prob.neutral | None | None | None | None | N |
| I/Y | 0.4413 | ambiguous | 0.3892 | ambiguous | -0.968 | Destabilizing | 0.204 | N | 0.565 | 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.