Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18582 | 55969;55970;55971 | chr2:178601160;178601159;178601158 | chr2:179465887;179465886;179465885 |
| N2AB | 16941 | 51046;51047;51048 | chr2:178601160;178601159;178601158 | chr2:179465887;179465886;179465885 |
| N2A | 16014 | 48265;48266;48267 | chr2:178601160;178601159;178601158 | chr2:179465887;179465886;179465885 |
| N2B | 9517 | 28774;28775;28776 | chr2:178601160;178601159;178601158 | chr2:179465887;179465886;179465885 |
| Novex-1 | 9642 | 29149;29150;29151 | chr2:178601160;178601159;178601158 | chr2:179465887;179465886;179465885 |
| Novex-2 | 9709 | 29350;29351;29352 | chr2:178601160;178601159;178601158 | chr2:179465887;179465886;179465885 |
| 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 | rs201194435  |
-0.894 | 0.142 | D | 0.699 | 0.414 | None | gnomAD-2.1.1 | 8.93E-05 | None | None | None | None | N | None | 4.34E-05 | 4.48E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.53175E-04 | 1.92086E-04 |
| P/L | rs201194435 |
-0.894 | 0.142 | D | 0.699 | 0.414 | None | gnomAD-3.1.2 | 9.21E-05 | None | None | None | None | N | None | 2.42E-05 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.7658E-04 | 0 | 0 |
| P/L | rs201194435 |
-0.894 | 0.142 | D | 0.699 | 0.414 | None | gnomAD-4.0.0 | 6.67409E-05 | None | None | None | None | N | None | 1.39427E-05 | 4.42674E-05 | None | 0 | 0 | None | 8.22368E-05 | 0 | 8.05453E-05 | 0 | 3.40692E-05 |
| P/S | rs1213775355 |
-1.947 | 0.994 | N | 0.861 | 0.367 | 0.314716216878 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14837E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs1213775355 |
-1.947 | 0.994 | N | 0.861 | 0.367 | 0.314716216878 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs1213775355 |
-1.947 | 0.994 | N | 0.861 | 0.367 | 0.314716216878 | gnomAD-4.0.0 | 6.57947E-06 | None | None | None | None | N | None | 2.41558E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1965 | likely_benign | 0.2061 | benign | -1.91 | Destabilizing | 0.958 | D | 0.803 | deleterious | N | 0.503295919 | None | None | N |
| P/C | 0.8269 | likely_pathogenic | 0.8506 | pathogenic | -1.445 | Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| P/D | 0.9562 | likely_pathogenic | 0.9589 | pathogenic | -2.461 | Highly Destabilizing | 0.998 | D | 0.865 | deleterious | None | None | None | None | N |
| P/E | 0.8223 | likely_pathogenic | 0.8436 | pathogenic | -2.403 | Highly Destabilizing | 0.995 | D | 0.866 | deleterious | None | None | None | None | N |
| P/F | 0.9426 | likely_pathogenic | 0.9393 | pathogenic | -1.365 | Destabilizing | 0.998 | D | 0.903 | deleterious | None | None | None | None | N |
| P/G | 0.8062 | likely_pathogenic | 0.8247 | pathogenic | -2.275 | Highly Destabilizing | 0.995 | D | 0.887 | deleterious | None | None | None | None | N |
| P/H | 0.7464 | likely_pathogenic | 0.7432 | pathogenic | -1.804 | Destabilizing | 0.999 | D | 0.903 | deleterious | N | 0.516494972 | None | None | N |
| P/I | 0.8419 | likely_pathogenic | 0.8427 | pathogenic | -0.963 | Destabilizing | 0.982 | D | 0.899 | deleterious | None | None | None | None | N |
| P/K | 0.8684 | likely_pathogenic | 0.8811 | pathogenic | -1.564 | Destabilizing | 0.995 | D | 0.873 | deleterious | None | None | None | None | N |
| P/L | 0.6803 | likely_pathogenic | 0.6338 | pathogenic | -0.963 | Destabilizing | 0.142 | N | 0.699 | prob.neutral | D | 0.522989432 | None | None | N |
| P/M | 0.8381 | likely_pathogenic | 0.8413 | pathogenic | -0.852 | Destabilizing | 0.998 | D | 0.913 | deleterious | None | None | None | None | N |
| P/N | 0.8791 | likely_pathogenic | 0.8922 | pathogenic | -1.548 | Destabilizing | 0.998 | D | 0.895 | deleterious | None | None | None | None | N |
| P/Q | 0.672 | likely_pathogenic | 0.6679 | pathogenic | -1.686 | Destabilizing | 0.998 | D | 0.867 | deleterious | None | None | None | None | N |
| P/R | 0.7673 | likely_pathogenic | 0.757 | pathogenic | -1.061 | Destabilizing | 0.994 | D | 0.891 | deleterious | N | 0.49209684 | None | None | N |
| P/S | 0.3995 | ambiguous | 0.4391 | ambiguous | -2.044 | Highly Destabilizing | 0.994 | D | 0.861 | deleterious | N | 0.47932173 | None | None | N |
| P/T | 0.5041 | ambiguous | 0.5239 | ambiguous | -1.884 | Destabilizing | 0.988 | D | 0.857 | deleterious | N | 0.501744852 | None | None | N |
| P/V | 0.7082 | likely_pathogenic | 0.703 | pathogenic | -1.249 | Destabilizing | 0.982 | D | 0.876 | deleterious | None | None | None | None | N |
| P/W | 0.9831 | likely_pathogenic | 0.981 | pathogenic | -1.667 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| P/Y | 0.9385 | likely_pathogenic | 0.9344 | pathogenic | -1.381 | Destabilizing | 0.999 | D | 0.907 | 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.