Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15754 | 47485;47486;47487 | chr2:178618198;178618197;178618196 | chr2:179482925;179482924;179482923 |
| N2AB | 14113 | 42562;42563;42564 | chr2:178618198;178618197;178618196 | chr2:179482925;179482924;179482923 |
| N2A | 13186 | 39781;39782;39783 | chr2:178618198;178618197;178618196 | chr2:179482925;179482924;179482923 |
| N2B | 6689 | 20290;20291;20292 | chr2:178618198;178618197;178618196 | chr2:179482925;179482924;179482923 |
| Novex-1 | 6814 | 20665;20666;20667 | chr2:178618198;178618197;178618196 | chr2:179482925;179482924;179482923 |
| Novex-2 | 6881 | 20866;20867;20868 | chr2:178618198;178618197;178618196 | chr2:179482925;179482924;179482923 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs775878082  |
0.073 | 0.021 | N | 0.14 | 0.094 | 0.16115917748 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.29E-05 | None | 0 | 0 | 0 |
| S/N | rs775878082 |
0.073 | 0.021 | N | 0.14 | 0.094 | 0.16115917748 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/N | rs775878082 |
0.073 | 0.021 | N | 0.14 | 0.094 | 0.16115917748 | gnomAD-4.0.0 | 2.56714E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39721E-06 | 1.34383E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2046 | likely_benign | 0.1849 | benign | -0.249 | Destabilizing | 0.927 | D | 0.557 | neutral | None | None | None | None | N |
| S/C | 0.262 | likely_benign | 0.2216 | benign | -0.283 | Destabilizing | 0.999 | D | 0.585 | neutral | N | 0.455943163 | None | None | N |
| S/D | 0.6392 | likely_pathogenic | 0.6059 | pathogenic | 0.28 | Stabilizing | 0.883 | D | 0.511 | neutral | None | None | None | None | N |
| S/E | 0.8057 | likely_pathogenic | 0.7948 | pathogenic | 0.176 | Stabilizing | 0.938 | D | 0.469 | neutral | None | None | None | None | N |
| S/F | 0.6861 | likely_pathogenic | 0.6298 | pathogenic | -0.955 | Destabilizing | 0.997 | D | 0.669 | prob.neutral | None | None | None | None | N |
| S/G | 0.1588 | likely_benign | 0.1382 | benign | -0.314 | Destabilizing | 0.824 | D | 0.508 | neutral | N | 0.469946496 | None | None | N |
| S/H | 0.666 | likely_pathogenic | 0.6424 | pathogenic | -0.702 | Destabilizing | 0.991 | D | 0.499 | neutral | None | None | None | None | N |
| S/I | 0.5508 | ambiguous | 0.4855 | ambiguous | -0.212 | Destabilizing | 0.996 | D | 0.706 | prob.delet. | N | 0.469411779 | None | None | N |
| S/K | 0.9317 | likely_pathogenic | 0.9195 | pathogenic | -0.318 | Destabilizing | 0.938 | D | 0.465 | neutral | None | None | None | None | N |
| S/L | 0.3287 | likely_benign | 0.2784 | benign | -0.212 | Destabilizing | 0.968 | D | 0.595 | neutral | None | None | None | None | N |
| S/M | 0.4735 | ambiguous | 0.4092 | ambiguous | -0.114 | Destabilizing | 0.999 | D | 0.501 | neutral | None | None | None | None | N |
| S/N | 0.199 | likely_benign | 0.1519 | benign | -0.047 | Destabilizing | 0.021 | N | 0.14 | neutral | N | 0.438658344 | None | None | N |
| S/P | 0.5296 | ambiguous | 0.4394 | ambiguous | -0.199 | Destabilizing | 0.997 | D | 0.582 | neutral | None | None | None | None | N |
| S/Q | 0.7771 | likely_pathogenic | 0.7507 | pathogenic | -0.267 | Destabilizing | 0.991 | D | 0.437 | neutral | None | None | None | None | N |
| S/R | 0.9071 | likely_pathogenic | 0.8926 | pathogenic | -0.109 | Destabilizing | 0.988 | D | 0.537 | neutral | N | 0.471129368 | None | None | N |
| S/T | 0.1874 | likely_benign | 0.163 | benign | -0.176 | Destabilizing | 0.824 | D | 0.582 | neutral | N | 0.393407447 | None | None | N |
| S/V | 0.5107 | ambiguous | 0.4566 | ambiguous | -0.199 | Destabilizing | 0.997 | D | 0.561 | neutral | None | None | None | None | N |
| S/W | 0.715 | likely_pathogenic | 0.6851 | pathogenic | -1.009 | Destabilizing | 0.999 | D | 0.816 | deleterious | None | None | None | None | N |
| S/Y | 0.5354 | ambiguous | 0.4921 | ambiguous | -0.7 | Destabilizing | 0.997 | D | 0.666 | prob.neutral | 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.