Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22265 | 67018;67019;67020 | chr2:178580586;178580585;178580584 | chr2:179445313;179445312;179445311 |
| N2AB | 20624 | 62095;62096;62097 | chr2:178580586;178580585;178580584 | chr2:179445313;179445312;179445311 |
| N2A | 19697 | 59314;59315;59316 | chr2:178580586;178580585;178580584 | chr2:179445313;179445312;179445311 |
| N2B | 13200 | 39823;39824;39825 | chr2:178580586;178580585;178580584 | chr2:179445313;179445312;179445311 |
| Novex-1 | 13325 | 40198;40199;40200 | chr2:178580586;178580585;178580584 | chr2:179445313;179445312;179445311 |
| Novex-2 | 13392 | 40399;40400;40401 | chr2:178580586;178580585;178580584 | chr2:179445313;179445312;179445311 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/E | rs750836266  |
-0.341 | 1.0 | N | 0.614 | 0.468 | 0.487912462561 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.68E-05 | None | 0 | None | 0 | 0 | 0 |
| A/E | rs750836266 |
-0.341 | 1.0 | N | 0.614 | 0.468 | 0.487912462561 | gnomAD-4.0.0 | 2.05737E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.53447E-05 | None | 0 | 0 | 1.80066E-06 | 0 | 0 |
| A/V | rs750836266 |
-0.036 | 1.0 | D | 0.599 | 0.378 | 0.423119698836 | gnomAD-2.1.1 | 1.76336E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.38955E-03 | None | 0 | 1.81E-05 | 0 |
| A/V | rs750836266 |
-0.036 | 1.0 | D | 0.599 | 0.378 | 0.423119698836 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 8.28844E-04 | 0 |
| A/V | rs750836266 |
-0.036 | 1.0 | D | 0.599 | 0.378 | 0.423119698836 | gnomAD-4.0.0 | 8.07281E-05 | None | None | None | None | I | None | 1.33547E-05 | 1.68073E-05 | None | 0 | 0 | None | 0 | 1.65563E-04 | 9.33252E-06 | 1.25533E-03 | 4.8151E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6382 | likely_pathogenic | 0.6516 | pathogenic | -0.817 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | I |
| A/D | 0.6421 | likely_pathogenic | 0.6894 | pathogenic | -0.565 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| A/E | 0.5792 | likely_pathogenic | 0.6246 | pathogenic | -0.709 | Destabilizing | 1.0 | D | 0.614 | neutral | N | 0.496907277 | None | None | I |
| A/F | 0.6207 | likely_pathogenic | 0.6509 | pathogenic | -0.85 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | I |
| A/G | 0.2387 | likely_benign | 0.2603 | benign | -0.229 | Destabilizing | 1.0 | D | 0.582 | neutral | N | 0.486564929 | None | None | I |
| A/H | 0.7332 | likely_pathogenic | 0.7566 | pathogenic | -0.192 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| A/I | 0.3962 | ambiguous | 0.4273 | ambiguous | -0.343 | Destabilizing | 1.0 | D | 0.603 | neutral | None | None | None | None | I |
| A/K | 0.7541 | likely_pathogenic | 0.7816 | pathogenic | -0.619 | Destabilizing | 1.0 | D | 0.611 | neutral | None | None | None | None | I |
| A/L | 0.2979 | likely_benign | 0.3228 | benign | -0.343 | Destabilizing | 1.0 | D | 0.581 | neutral | None | None | None | None | I |
| A/M | 0.3572 | ambiguous | 0.3846 | ambiguous | -0.577 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | I |
| A/N | 0.4591 | ambiguous | 0.4995 | ambiguous | -0.304 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | I |
| A/P | 0.3006 | likely_benign | 0.3485 | ambiguous | -0.271 | Destabilizing | 1.0 | D | 0.615 | neutral | N | 0.498174724 | None | None | I |
| A/Q | 0.5696 | likely_pathogenic | 0.5988 | pathogenic | -0.56 | Destabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | I |
| A/R | 0.6868 | likely_pathogenic | 0.7073 | pathogenic | -0.173 | Destabilizing | 1.0 | D | 0.625 | neutral | None | None | None | None | I |
| A/S | 0.1339 | likely_benign | 0.1434 | benign | -0.48 | Destabilizing | 1.0 | D | 0.607 | neutral | D | 0.525186635 | None | None | I |
| A/T | 0.1572 | likely_benign | 0.173 | benign | -0.552 | Destabilizing | 1.0 | D | 0.617 | neutral | D | 0.525629353 | None | None | I |
| A/V | 0.1947 | likely_benign | 0.2239 | benign | -0.271 | Destabilizing | 1.0 | D | 0.599 | neutral | D | 0.531957892 | None | None | I |
| A/W | 0.8893 | likely_pathogenic | 0.8888 | pathogenic | -0.973 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| A/Y | 0.7068 | likely_pathogenic | 0.7268 | pathogenic | -0.649 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | 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.