Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8794 | 26605;26606;26607 | chr2:178714394;178714393;178714392 | chr2:179579121;179579120;179579119 |
| N2AB | 8477 | 25654;25655;25656 | chr2:178714394;178714393;178714392 | chr2:179579121;179579120;179579119 |
| N2A | 7550 | 22873;22874;22875 | chr2:178714394;178714393;178714392 | chr2:179579121;179579120;179579119 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/I | None | 0.057 | 0.165 | D | 0.633 | 0.258 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| L/I | None | 0.057 | 0.165 | D | 0.633 | 0.258 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| L/I | None | 0.057 | 0.165 | D | 0.633 | 0.258 | None | gnomAD-4.0.0 | 3.09861E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23819E-06 | 0 | 0 |
| L/V | rs372229450  |
-0.582 | 0.005 | D | 0.439 | 0.289 | 0.555987101472 | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.58607E-04 | None | 0 | None | 0 | 0 | 0 |
| L/V | rs372229450 |
-0.582 | 0.005 | D | 0.439 | 0.289 | 0.555987101472 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 5.78258E-04 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | rs372229450 |
-0.582 | 0.005 | D | 0.439 | 0.289 | 0.555987101472 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| L/V | rs372229450 |
-0.582 | 0.005 | D | 0.439 | 0.289 | 0.555987101472 | gnomAD-4.0.0 | 1.79706E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.23969E-04 | None | 0 | 0 | 8.47643E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.7956 | likely_pathogenic | 0.8836 | pathogenic | -2.079 | Highly Destabilizing | 0.963 | D | 0.707 | prob.neutral | None | None | None | None | N |
| L/C | 0.7906 | likely_pathogenic | 0.8863 | pathogenic | -1.398 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| L/D | 0.9986 | likely_pathogenic | 0.9994 | pathogenic | -2.962 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| L/E | 0.9866 | likely_pathogenic | 0.9934 | pathogenic | -2.658 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| L/F | 0.2976 | likely_benign | 0.4694 | ambiguous | -1.354 | Destabilizing | 0.982 | D | 0.698 | prob.neutral | D | 0.545563226 | None | None | N |
| L/G | 0.9561 | likely_pathogenic | 0.9772 | pathogenic | -2.623 | Highly Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| L/H | 0.9513 | likely_pathogenic | 0.9772 | pathogenic | -2.63 | Highly Destabilizing | 0.999 | D | 0.851 | deleterious | None | None | None | None | N |
| L/I | 0.163 | likely_benign | 0.223 | benign | -0.438 | Destabilizing | 0.165 | N | 0.633 | neutral | D | 0.536813814 | None | None | N |
| L/K | 0.9767 | likely_pathogenic | 0.9873 | pathogenic | -1.642 | Destabilizing | 0.994 | D | 0.845 | deleterious | None | None | None | None | N |
| L/M | 0.1733 | likely_benign | 0.2402 | benign | -0.718 | Destabilizing | 0.561 | D | 0.578 | neutral | None | None | None | None | N |
| L/N | 0.9892 | likely_pathogenic | 0.9941 | pathogenic | -2.403 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| L/P | 0.9913 | likely_pathogenic | 0.995 | pathogenic | -0.978 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| L/Q | 0.9207 | likely_pathogenic | 0.9585 | pathogenic | -1.984 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| L/R | 0.9409 | likely_pathogenic | 0.9688 | pathogenic | -1.982 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| L/S | 0.9516 | likely_pathogenic | 0.9798 | pathogenic | -2.792 | Highly Destabilizing | 1.0 | D | 0.839 | deleterious | D | 0.574089189 | None | None | N |
| L/T | 0.8982 | likely_pathogenic | 0.9503 | pathogenic | -2.326 | Highly Destabilizing | 0.982 | D | 0.775 | deleterious | None | None | None | None | N |
| L/V | 0.1712 | likely_benign | 0.2125 | benign | -0.978 | Destabilizing | 0.005 | N | 0.439 | neutral | D | 0.560958457 | None | None | N |
| L/W | 0.8292 | likely_pathogenic | 0.9294 | pathogenic | -1.719 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| L/Y | 0.8696 | likely_pathogenic | 0.9337 | pathogenic | -1.492 | Destabilizing | 0.945 | D | 0.769 | deleterious | 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.