Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21942 | 66049;66050;66051 | chr2:178582979;178582978;178582977 | chr2:179447706;179447705;179447704 |
| N2AB | 20301 | 61126;61127;61128 | chr2:178582979;178582978;178582977 | chr2:179447706;179447705;179447704 |
| N2A | 19374 | 58345;58346;58347 | chr2:178582979;178582978;178582977 | chr2:179447706;179447705;179447704 |
| N2B | 12877 | 38854;38855;38856 | chr2:178582979;178582978;178582977 | chr2:179447706;179447705;179447704 |
| Novex-1 | 13002 | 39229;39230;39231 | chr2:178582979;178582978;178582977 | chr2:179447706;179447705;179447704 |
| Novex-2 | 13069 | 39430;39431;39432 | chr2:178582979;178582978;178582977 | chr2:179447706;179447705;179447704 |
| 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/G | None | None | 0.454 | N | 0.35 | 0.154 | 0.279776271856 | gnomAD-4.0.0 | 1.42604E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.26063E-07 | 0 | 1.73322E-05 |
| S/N | rs1274120348  |
0.127 | 0.022 | N | 0.205 | 0.114 | 0.242825505644 | gnomAD-2.1.1 | 4.44E-06 | None | None | None | None | I | None | 0 | 0 | None | 1.15527E-04 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/N | rs1274120348 |
0.127 | 0.022 | N | 0.205 | 0.114 | 0.242825505644 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 2.41E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | rs1274120348 |
0.127 | 0.022 | N | 0.205 | 0.114 | 0.242825505644 | gnomAD-4.0.0 | 2.57514E-06 | None | None | None | None | I | None | 2.74175E-05 | 1.85694E-05 | None | 3.61063E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0937 | likely_benign | 0.0972 | benign | -0.277 | Destabilizing | 0.007 | N | 0.203 | neutral | None | None | None | None | I |
| S/C | 0.0906 | likely_benign | 0.0929 | benign | -0.285 | Destabilizing | 0.991 | D | 0.508 | neutral | N | 0.504776865 | None | None | I |
| S/D | 0.824 | likely_pathogenic | 0.7844 | pathogenic | -0.088 | Destabilizing | 0.728 | D | 0.31 | neutral | None | None | None | None | I |
| S/E | 0.8725 | likely_pathogenic | 0.8477 | pathogenic | -0.201 | Destabilizing | 0.842 | D | 0.315 | neutral | None | None | None | None | I |
| S/F | 0.3392 | likely_benign | 0.332 | benign | -1.062 | Destabilizing | 0.016 | N | 0.455 | neutral | None | None | None | None | I |
| S/G | 0.1598 | likely_benign | 0.1651 | benign | -0.285 | Destabilizing | 0.454 | N | 0.35 | neutral | N | 0.471066936 | None | None | I |
| S/H | 0.5974 | likely_pathogenic | 0.5327 | ambiguous | -0.714 | Destabilizing | 0.974 | D | 0.505 | neutral | None | None | None | None | I |
| S/I | 0.331 | likely_benign | 0.312 | benign | -0.376 | Destabilizing | 0.934 | D | 0.558 | neutral | N | 0.454462688 | None | None | I |
| S/K | 0.9474 | likely_pathogenic | 0.9182 | pathogenic | -0.328 | Destabilizing | 0.842 | D | 0.316 | neutral | None | None | None | None | I |
| S/L | 0.1922 | likely_benign | 0.1755 | benign | -0.376 | Destabilizing | 0.728 | D | 0.504 | neutral | None | None | None | None | I |
| S/M | 0.3365 | likely_benign | 0.3118 | benign | -0.152 | Destabilizing | 0.991 | D | 0.501 | neutral | None | None | None | None | I |
| S/N | 0.3582 | ambiguous | 0.3313 | benign | -0.082 | Destabilizing | 0.022 | N | 0.205 | neutral | N | 0.448846224 | None | None | I |
| S/P | 0.9063 | likely_pathogenic | 0.9034 | pathogenic | -0.323 | Destabilizing | 0.974 | D | 0.481 | neutral | None | None | None | None | I |
| S/Q | 0.7933 | likely_pathogenic | 0.745 | pathogenic | -0.324 | Destabilizing | 0.974 | D | 0.396 | neutral | None | None | None | None | I |
| S/R | 0.8906 | likely_pathogenic | 0.8441 | pathogenic | -0.155 | Destabilizing | 0.966 | D | 0.459 | neutral | N | 0.493655794 | None | None | I |
| S/T | 0.1612 | likely_benign | 0.1481 | benign | -0.195 | Destabilizing | 0.625 | D | 0.323 | neutral | N | 0.489055264 | None | None | I |
| S/V | 0.2757 | likely_benign | 0.2668 | benign | -0.323 | Destabilizing | 0.728 | D | 0.515 | neutral | None | None | None | None | I |
| S/W | 0.5856 | likely_pathogenic | 0.5233 | ambiguous | -1.137 | Destabilizing | 0.998 | D | 0.598 | neutral | None | None | None | None | I |
| S/Y | 0.3866 | ambiguous | 0.3479 | ambiguous | -0.835 | Destabilizing | 0.904 | D | 0.585 | neutral | 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.