Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6227 | 18904;18905;18906 | chr2:178729477;178729476;178729475 | chr2:179594204;179594203;179594202 |
| N2AB | 5910 | 17953;17954;17955 | chr2:178729477;178729476;178729475 | chr2:179594204;179594203;179594202 |
| N2A | 4983 | 15172;15173;15174 | chr2:178729477;178729476;178729475 | chr2:179594204;179594203;179594202 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs376846228  |
0.123 | 1.0 | N | 0.685 | 0.462 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | I | None | 4.13E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.57E-05 | 0 |
| P/L | rs376846228 |
0.123 | 1.0 | N | 0.685 | 0.462 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| P/L | rs376846228 |
0.123 | 1.0 | N | 0.685 | 0.462 | None | gnomAD-4.0.0 | 8.05746E-06 | None | None | None | None | I | None | 6.67931E-05 | 0 | None | 3.38021E-05 | 0 | None | 0 | 0 | 4.23857E-06 | 1.09794E-05 | 1.60128E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1212 | likely_benign | 0.1314 | benign | -0.575 | Destabilizing | 1.0 | D | 0.661 | neutral | D | 0.534923626 | None | None | I |
| P/C | 0.6629 | likely_pathogenic | 0.7192 | pathogenic | -0.597 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| P/D | 0.4772 | ambiguous | 0.486 | ambiguous | -0.59 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | I |
| P/E | 0.3689 | ambiguous | 0.3499 | ambiguous | -0.674 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | I |
| P/F | 0.5773 | likely_pathogenic | 0.6287 | pathogenic | -0.691 | Destabilizing | 1.0 | D | 0.627 | neutral | None | None | None | None | I |
| P/G | 0.4063 | ambiguous | 0.4478 | ambiguous | -0.728 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | I |
| P/H | 0.2973 | likely_benign | 0.3179 | benign | -0.226 | Destabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | I |
| P/I | 0.3863 | ambiguous | 0.4179 | ambiguous | -0.3 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
| P/K | 0.4454 | ambiguous | 0.4277 | ambiguous | -0.577 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | I |
| P/L | 0.1889 | likely_benign | 0.2001 | benign | -0.3 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | N | 0.490149782 | None | None | I |
| P/M | 0.4415 | ambiguous | 0.4738 | ambiguous | -0.49 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | I |
| P/N | 0.4197 | ambiguous | 0.4529 | ambiguous | -0.32 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| P/Q | 0.2589 | likely_benign | 0.2581 | benign | -0.54 | Destabilizing | 1.0 | D | 0.638 | neutral | D | 0.527688223 | None | None | I |
| P/R | 0.2706 | likely_benign | 0.2617 | benign | -0.055 | Destabilizing | 1.0 | D | 0.669 | neutral | D | 0.528883088 | None | None | I |
| P/S | 0.1817 | likely_benign | 0.2019 | benign | -0.638 | Destabilizing | 1.0 | D | 0.674 | neutral | N | 0.490212234 | None | None | I |
| P/T | 0.1638 | likely_benign | 0.1772 | benign | -0.625 | Destabilizing | 1.0 | D | 0.668 | neutral | N | 0.520396891 | None | None | I |
| P/V | 0.2734 | likely_benign | 0.2943 | benign | -0.359 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| P/W | 0.7835 | likely_pathogenic | 0.7939 | pathogenic | -0.791 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | I |
| P/Y | 0.5512 | ambiguous | 0.5903 | pathogenic | -0.502 | Destabilizing | 1.0 | D | 0.637 | 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.