Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20330 | 61213;61214;61215 | chr2:178590737;178590736;178590735 | chr2:179455464;179455463;179455462 |
| N2AB | 18689 | 56290;56291;56292 | chr2:178590737;178590736;178590735 | chr2:179455464;179455463;179455462 |
| N2A | 17762 | 53509;53510;53511 | chr2:178590737;178590736;178590735 | chr2:179455464;179455463;179455462 |
| N2B | 11265 | 34018;34019;34020 | chr2:178590737;178590736;178590735 | chr2:179455464;179455463;179455462 |
| Novex-1 | 11390 | 34393;34394;34395 | chr2:178590737;178590736;178590735 | chr2:179455464;179455463;179455462 |
| Novex-2 | 11457 | 34594;34595;34596 | chr2:178590737;178590736;178590735 | chr2:179455464;179455463;179455462 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/C | rs780137240  |
-1.454 | 0.999 | N | 0.681 | 0.372 | 0.321951552304 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.3E-05 | None | 0 | 0 | 0 |
| F/C | rs780137240 |
-1.454 | 0.999 | N | 0.681 | 0.372 | 0.321951552304 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 7.32654E-05 |
| F/L | rs2050031384 |
-1.377 | 0.64 | N | 0.451 | 0.347 | 0.171388866994 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.97837E-04 | None | 0 | 0 | 0 |
| F/L | rs2050031384 |
-1.377 | 0.64 | N | 0.451 | 0.347 | 0.171388866994 | gnomAD-4.0.0 | 9.58986E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.39532E-04 | 3.31741E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.6724 | likely_pathogenic | 0.6488 | pathogenic | -2.419 | Highly Destabilizing | 0.919 | D | 0.549 | neutral | None | None | None | None | N |
| F/C | 0.2361 | likely_benign | 0.2193 | benign | -1.577 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | N | 0.46649533 | None | None | N |
| F/D | 0.9256 | likely_pathogenic | 0.896 | pathogenic | -2.204 | Highly Destabilizing | 0.996 | D | 0.683 | prob.neutral | None | None | None | None | N |
| F/E | 0.8973 | likely_pathogenic | 0.878 | pathogenic | -2.052 | Highly Destabilizing | 0.988 | D | 0.663 | neutral | None | None | None | None | N |
| F/G | 0.8167 | likely_pathogenic | 0.7714 | pathogenic | -2.8 | Highly Destabilizing | 0.988 | D | 0.636 | neutral | None | None | None | None | N |
| F/H | 0.5598 | ambiguous | 0.5153 | ambiguous | -1.067 | Destabilizing | 0.976 | D | 0.585 | neutral | None | None | None | None | N |
| F/I | 0.2797 | likely_benign | 0.2778 | benign | -1.219 | Destabilizing | 0.896 | D | 0.432 | neutral | N | 0.497586242 | None | None | N |
| F/K | 0.8818 | likely_pathogenic | 0.8616 | pathogenic | -1.957 | Destabilizing | 0.988 | D | 0.666 | neutral | None | None | None | None | N |
| F/L | 0.8046 | likely_pathogenic | 0.7643 | pathogenic | -1.219 | Destabilizing | 0.64 | D | 0.451 | neutral | N | 0.500509117 | None | None | N |
| F/M | 0.4393 | ambiguous | 0.4269 | ambiguous | -0.921 | Destabilizing | 0.996 | D | 0.457 | neutral | None | None | None | None | N |
| F/N | 0.7519 | likely_pathogenic | 0.6974 | pathogenic | -2.308 | Highly Destabilizing | 0.988 | D | 0.699 | prob.neutral | None | None | None | None | N |
| F/P | 0.9968 | likely_pathogenic | 0.9956 | pathogenic | -1.622 | Destabilizing | 0.996 | D | 0.728 | prob.delet. | None | None | None | None | N |
| F/Q | 0.7812 | likely_pathogenic | 0.7479 | pathogenic | -2.298 | Highly Destabilizing | 0.996 | D | 0.721 | prob.delet. | None | None | None | None | N |
| F/R | 0.8179 | likely_pathogenic | 0.7948 | pathogenic | -1.358 | Destabilizing | 0.988 | D | 0.711 | prob.delet. | None | None | None | None | N |
| F/S | 0.5947 | likely_pathogenic | 0.5647 | pathogenic | -2.97 | Highly Destabilizing | 0.984 | D | 0.592 | neutral | N | 0.493805134 | None | None | N |
| F/T | 0.6463 | likely_pathogenic | 0.6318 | pathogenic | -2.714 | Highly Destabilizing | 0.988 | D | 0.593 | neutral | None | None | None | None | N |
| F/V | 0.2676 | likely_benign | 0.2719 | benign | -1.622 | Destabilizing | 0.896 | D | 0.465 | neutral | N | 0.498620818 | None | None | N |
| F/W | 0.4358 | ambiguous | 0.3804 | ambiguous | -0.321 | Destabilizing | 0.988 | D | 0.46 | neutral | None | None | None | None | N |
| F/Y | 0.0957 | likely_benign | 0.0776 | benign | -0.636 | Destabilizing | 0.004 | N | 0.153 | neutral | N | 0.413484778 | 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.