Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18937 | 57034;57035;57036 | chr2:178598901;178598900;178598899 | chr2:179463628;179463627;179463626 |
| N2AB | 17296 | 52111;52112;52113 | chr2:178598901;178598900;178598899 | chr2:179463628;179463627;179463626 |
| N2A | 16369 | 49330;49331;49332 | chr2:178598901;178598900;178598899 | chr2:179463628;179463627;179463626 |
| N2B | 9872 | 29839;29840;29841 | chr2:178598901;178598900;178598899 | chr2:179463628;179463627;179463626 |
| Novex-1 | 9997 | 30214;30215;30216 | chr2:178598901;178598900;178598899 | chr2:179463628;179463627;179463626 |
| Novex-2 | 10064 | 30415;30416;30417 | chr2:178598901;178598900;178598899 | chr2:179463628;179463627;179463626 |
| 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/G | None | None | 0.996 | N | 0.626 | 0.495 | 0.233785782151 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/H | rs779010234  |
0.134 | 1.0 | N | 0.663 | 0.413 | 0.29385284311 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| D/H | rs779010234 |
0.134 | 1.0 | N | 0.663 | 0.413 | 0.29385284311 | gnomAD-4.0.0 | 1.59249E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.7818E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4696 | ambiguous | 0.4258 | ambiguous | -0.18 | Destabilizing | 0.998 | D | 0.621 | neutral | N | 0.471362432 | None | None | I |
| D/C | 0.8986 | likely_pathogenic | 0.8705 | pathogenic | -0.291 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| D/E | 0.1947 | likely_benign | 0.1738 | benign | -0.315 | Destabilizing | 0.619 | D | 0.287 | neutral | N | 0.434382912 | None | None | I |
| D/F | 0.7862 | likely_pathogenic | 0.7482 | pathogenic | 0.01 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| D/G | 0.6067 | likely_pathogenic | 0.5416 | ambiguous | -0.368 | Destabilizing | 0.996 | D | 0.626 | neutral | N | 0.442983752 | None | None | I |
| D/H | 0.6654 | likely_pathogenic | 0.5945 | pathogenic | 0.525 | Stabilizing | 1.0 | D | 0.663 | neutral | N | 0.485870525 | None | None | I |
| D/I | 0.645 | likely_pathogenic | 0.5644 | pathogenic | 0.268 | Stabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| D/K | 0.7609 | likely_pathogenic | 0.6931 | pathogenic | 0.238 | Stabilizing | 0.998 | D | 0.645 | neutral | None | None | None | None | I |
| D/L | 0.6644 | likely_pathogenic | 0.5898 | pathogenic | 0.268 | Stabilizing | 0.999 | D | 0.698 | prob.neutral | None | None | None | None | I |
| D/M | 0.8117 | likely_pathogenic | 0.7699 | pathogenic | 0.09 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| D/N | 0.2651 | likely_benign | 0.2447 | benign | -0.184 | Destabilizing | 0.999 | D | 0.623 | neutral | N | 0.434345627 | None | None | I |
| D/P | 0.9652 | likely_pathogenic | 0.9567 | pathogenic | 0.14 | Stabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | I |
| D/Q | 0.6374 | likely_pathogenic | 0.5604 | ambiguous | -0.128 | Destabilizing | 0.998 | D | 0.667 | neutral | None | None | None | None | I |
| D/R | 0.8149 | likely_pathogenic | 0.7613 | pathogenic | 0.6 | Stabilizing | 0.998 | D | 0.665 | neutral | None | None | None | None | I |
| D/S | 0.3537 | ambiguous | 0.3219 | benign | -0.283 | Destabilizing | 0.994 | D | 0.563 | neutral | None | None | None | None | I |
| D/T | 0.5043 | ambiguous | 0.4493 | ambiguous | -0.124 | Destabilizing | 0.999 | D | 0.682 | prob.neutral | None | None | None | None | I |
| D/V | 0.4595 | ambiguous | 0.3853 | ambiguous | 0.14 | Stabilizing | 0.999 | D | 0.701 | prob.neutral | N | 0.437865934 | None | None | I |
| D/W | 0.9646 | likely_pathogenic | 0.9529 | pathogenic | 0.152 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | I |
| D/Y | 0.4904 | ambiguous | 0.3981 | ambiguous | 0.255 | Stabilizing | 1.0 | D | 0.702 | prob.neutral | N | 0.478136476 | 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.