Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19973 | 60142;60143;60144 | chr2:178591987;178591986;178591985 | chr2:179456714;179456713;179456712 |
| N2AB | 18332 | 55219;55220;55221 | chr2:178591987;178591986;178591985 | chr2:179456714;179456713;179456712 |
| N2A | 17405 | 52438;52439;52440 | chr2:178591987;178591986;178591985 | chr2:179456714;179456713;179456712 |
| N2B | 10908 | 32947;32948;32949 | chr2:178591987;178591986;178591985 | chr2:179456714;179456713;179456712 |
| Novex-1 | 11033 | 33322;33323;33324 | chr2:178591987;178591986;178591985 | chr2:179456714;179456713;179456712 |
| Novex-2 | 11100 | 33523;33524;33525 | chr2:178591987;178591986;178591985 | chr2:179456714;179456713;179456712 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs148353350  |
0.342 | 0.06 | N | 0.225 | 0.206 | None | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.1288E-04 | None | 6.59E-05 | None | 0 | 0 | 0 |
| D/N | rs148353350 |
0.342 | 0.06 | N | 0.225 | 0.206 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93723E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs148353350 |
0.342 | 0.06 | N | 0.225 | 0.206 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| D/N | rs148353350 |
0.342 | 0.06 | N | 0.225 | 0.206 | None | gnomAD-4.0.0 | 5.58149E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.48009E-05 | None | 0 | 0 | 0 | 6.60997E-05 | 1.602E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7194 | likely_pathogenic | 0.7902 | pathogenic | -0.438 | Destabilizing | 0.958 | D | 0.567 | neutral | N | 0.507450945 | None | None | N |
| D/C | 0.9568 | likely_pathogenic | 0.9739 | pathogenic | -0.264 | Destabilizing | 0.999 | D | 0.856 | deleterious | None | None | None | None | N |
| D/E | 0.6901 | likely_pathogenic | 0.7264 | pathogenic | -0.488 | Destabilizing | 0.824 | D | 0.588 | neutral | N | 0.488307823 | None | None | N |
| D/F | 0.9016 | likely_pathogenic | 0.9435 | pathogenic | -0.196 | Destabilizing | 0.997 | D | 0.734 | deleterious | None | None | None | None | N |
| D/G | 0.8699 | likely_pathogenic | 0.9109 | pathogenic | -0.681 | Destabilizing | 0.919 | D | 0.656 | prob.neutral | N | 0.505989507 | None | None | N |
| D/H | 0.7698 | likely_pathogenic | 0.8495 | pathogenic | -0.094 | Destabilizing | 0.988 | D | 0.588 | neutral | N | 0.508491095 | None | None | N |
| D/I | 0.9049 | likely_pathogenic | 0.9459 | pathogenic | 0.171 | Stabilizing | 0.997 | D | 0.791 | deleterious | None | None | None | None | N |
| D/K | 0.9481 | likely_pathogenic | 0.9669 | pathogenic | -0.123 | Destabilizing | 0.938 | D | 0.67 | prob.neutral | None | None | None | None | N |
| D/L | 0.84 | likely_pathogenic | 0.8851 | pathogenic | 0.171 | Stabilizing | 0.991 | D | 0.771 | deleterious | None | None | None | None | N |
| D/M | 0.9585 | likely_pathogenic | 0.9765 | pathogenic | 0.289 | Stabilizing | 0.999 | D | 0.793 | deleterious | None | None | None | None | N |
| D/N | 0.4832 | ambiguous | 0.5678 | pathogenic | -0.493 | Destabilizing | 0.06 | N | 0.225 | neutral | N | 0.469626062 | None | None | N |
| D/P | 0.9264 | likely_pathogenic | 0.9397 | pathogenic | -0.009 | Destabilizing | 0.997 | D | 0.649 | prob.neutral | None | None | None | None | N |
| D/Q | 0.8919 | likely_pathogenic | 0.9269 | pathogenic | -0.422 | Destabilizing | 0.991 | D | 0.635 | neutral | None | None | None | None | N |
| D/R | 0.9425 | likely_pathogenic | 0.9635 | pathogenic | 0.164 | Stabilizing | 0.991 | D | 0.753 | deleterious | None | None | None | None | N |
| D/S | 0.5691 | likely_pathogenic | 0.649 | pathogenic | -0.619 | Destabilizing | 0.938 | D | 0.639 | neutral | None | None | None | None | N |
| D/T | 0.8637 | likely_pathogenic | 0.9193 | pathogenic | -0.431 | Destabilizing | 0.938 | D | 0.672 | prob.neutral | None | None | None | None | N |
| D/V | 0.817 | likely_pathogenic | 0.8863 | pathogenic | -0.009 | Destabilizing | 0.996 | D | 0.797 | deleterious | N | 0.478919066 | None | None | N |
| D/W | 0.9748 | likely_pathogenic | 0.984 | pathogenic | -0.027 | Destabilizing | 0.999 | D | 0.875 | deleterious | None | None | None | None | N |
| D/Y | 0.6344 | likely_pathogenic | 0.733 | pathogenic | 0.027 | Stabilizing | 0.996 | D | 0.749 | deleterious | N | 0.508144378 | 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.