Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25390 | 76393;76394;76395 | chr2:178569964;178569963;178569962 | chr2:179434691;179434690;179434689 |
| N2AB | 23749 | 71470;71471;71472 | chr2:178569964;178569963;178569962 | chr2:179434691;179434690;179434689 |
| N2A | 22822 | 68689;68690;68691 | chr2:178569964;178569963;178569962 | chr2:179434691;179434690;179434689 |
| N2B | 16325 | 49198;49199;49200 | chr2:178569964;178569963;178569962 | chr2:179434691;179434690;179434689 |
| Novex-1 | 16450 | 49573;49574;49575 | chr2:178569964;178569963;178569962 | chr2:179434691;179434690;179434689 |
| Novex-2 | 16517 | 49774;49775;49776 | chr2:178569964;178569963;178569962 | chr2:179434691;179434690;179434689 |
| 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 | rs775467614  |
-0.701 | 0.976 | N | 0.78 | 0.501 | 0.551467209619 | gnomAD-2.1.1 | 8.1E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.61E-05 | None | 3.28E-05 | None | 0 | 0 | 0 |
| P/L | rs775467614 |
-0.701 | 0.976 | N | 0.78 | 0.501 | 0.551467209619 | gnomAD-4.0.0 | 3.19006E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.78118E-05 | None | 0 | 0 | 0 | 1.43546E-05 | 0 |
| P/S | rs878948198 |
-1.078 | 0.976 | N | 0.696 | 0.418 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| P/S | rs878948198 |
-1.078 | 0.976 | N | 0.696 | 0.418 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| P/S | rs878948198 |
-1.078 | 0.976 | N | 0.696 | 0.418 | None | gnomAD-4.0.0 | 5.08679E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.70153E-05 | 0 | 4.80846E-05 |
| P/T | None | None | 0.988 | N | 0.704 | 0.449 | 0.417081434665 | gnomAD-4.0.0 | 2.05472E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.70057E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0758 | likely_benign | 0.0768 | benign | -1.5 | Destabilizing | 0.067 | N | 0.471 | neutral | N | 0.518305443 | None | None | I |
| P/C | 0.4874 | ambiguous | 0.5165 | ambiguous | -1.1 | Destabilizing | 0.999 | D | 0.875 | deleterious | None | None | None | None | I |
| P/D | 0.793 | likely_pathogenic | 0.7407 | pathogenic | -1.649 | Destabilizing | 0.995 | D | 0.77 | deleterious | None | None | None | None | I |
| P/E | 0.6267 | likely_pathogenic | 0.5796 | pathogenic | -1.699 | Destabilizing | 0.991 | D | 0.755 | deleterious | None | None | None | None | I |
| P/F | 0.4243 | ambiguous | 0.4224 | ambiguous | -1.423 | Destabilizing | 0.999 | D | 0.883 | deleterious | None | None | None | None | I |
| P/G | 0.4845 | ambiguous | 0.4318 | ambiguous | -1.743 | Destabilizing | 0.938 | D | 0.71 | prob.delet. | None | None | None | None | I |
| P/H | 0.3518 | ambiguous | 0.3297 | benign | -1.219 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | I |
| P/I | 0.3721 | ambiguous | 0.3461 | ambiguous | -0.945 | Destabilizing | 0.991 | D | 0.855 | deleterious | None | None | None | None | I |
| P/K | 0.655 | likely_pathogenic | 0.6079 | pathogenic | -1.121 | Destabilizing | 0.991 | D | 0.771 | deleterious | None | None | None | None | I |
| P/L | 0.1862 | likely_benign | 0.1629 | benign | -0.945 | Destabilizing | 0.976 | D | 0.78 | deleterious | N | 0.494002036 | None | None | I |
| P/M | 0.3676 | ambiguous | 0.3618 | ambiguous | -0.697 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | I |
| P/N | 0.5959 | likely_pathogenic | 0.5599 | ambiguous | -0.92 | Destabilizing | 0.995 | D | 0.832 | deleterious | None | None | None | None | I |
| P/Q | 0.3644 | ambiguous | 0.3318 | benign | -1.223 | Destabilizing | 0.994 | D | 0.809 | deleterious | D | 0.525490512 | None | None | I |
| P/R | 0.5059 | ambiguous | 0.4338 | ambiguous | -0.527 | Destabilizing | 0.994 | D | 0.831 | deleterious | N | 0.506879278 | None | None | I |
| P/S | 0.2142 | likely_benign | 0.1946 | benign | -1.36 | Destabilizing | 0.976 | D | 0.696 | prob.neutral | N | 0.496826419 | None | None | I |
| P/T | 0.2069 | likely_benign | 0.1842 | benign | -1.316 | Destabilizing | 0.988 | D | 0.704 | prob.neutral | N | 0.520464083 | None | None | I |
| P/V | 0.2447 | likely_benign | 0.2263 | benign | -1.097 | Destabilizing | 0.982 | D | 0.721 | prob.delet. | None | None | None | None | I |
| P/W | 0.7392 | likely_pathogenic | 0.6852 | pathogenic | -1.511 | Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | I |
| P/Y | 0.4674 | ambiguous | 0.4548 | ambiguous | -1.233 | Destabilizing | 1.0 | D | 0.883 | deleterious | 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.