Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26333 | 79222;79223;79224 | chr2:178567135;178567134;178567133 | chr2:179431862;179431861;179431860 |
| N2AB | 24692 | 74299;74300;74301 | chr2:178567135;178567134;178567133 | chr2:179431862;179431861;179431860 |
| N2A | 23765 | 71518;71519;71520 | chr2:178567135;178567134;178567133 | chr2:179431862;179431861;179431860 |
| N2B | 17268 | 52027;52028;52029 | chr2:178567135;178567134;178567133 | chr2:179431862;179431861;179431860 |
| Novex-1 | 17393 | 52402;52403;52404 | chr2:178567135;178567134;178567133 | chr2:179431862;179431861;179431860 |
| Novex-2 | 17460 | 52603;52604;52605 | chr2:178567135;178567134;178567133 | chr2:179431862;179431861;179431860 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | None | None | 0.638 | N | 0.542 | 0.347 | 0.506673610527 | gnomAD-4.0.0 | 1.36862E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31895E-05 | 0 |
| A/S | rs1221437302  |
-0.42 | 0.201 | N | 0.387 | 0.106 | 0.146414634003 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| A/S | rs1221437302 |
-0.42 | 0.201 | N | 0.387 | 0.106 | 0.146414634003 | gnomAD-4.0.0 | 3.1836E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.54939E-05 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | None | None | 0.002 | N | 0.263 | 0.087 | 0.171388866994 | gnomAD-4.0.0 | 3.1836E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71883E-06 | 0 | 0 |
| A/V | None | None | 0.002 | N | 0.277 | 0.234 | 0.311691414656 | gnomAD-4.0.0 | 6.84309E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9959E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6811 | likely_pathogenic | 0.7001 | pathogenic | -0.624 | Destabilizing | 0.947 | D | 0.391 | neutral | None | None | None | None | I |
| A/D | 0.958 | likely_pathogenic | 0.9686 | pathogenic | -0.567 | Destabilizing | 0.638 | D | 0.542 | neutral | N | 0.477458899 | None | None | I |
| A/E | 0.9213 | likely_pathogenic | 0.9358 | pathogenic | -0.665 | Destabilizing | 0.7 | D | 0.397 | neutral | None | None | None | None | I |
| A/F | 0.7311 | likely_pathogenic | 0.7309 | pathogenic | -0.826 | Destabilizing | 0.7 | D | 0.55 | neutral | None | None | None | None | I |
| A/G | 0.4416 | ambiguous | 0.4859 | ambiguous | -0.612 | Destabilizing | 0.334 | N | 0.346 | neutral | N | 0.452216524 | None | None | I |
| A/H | 0.9008 | likely_pathogenic | 0.8935 | pathogenic | -0.622 | Destabilizing | 0.982 | D | 0.586 | neutral | None | None | None | None | I |
| A/I | 0.4867 | ambiguous | 0.5344 | ambiguous | -0.292 | Destabilizing | 0.25 | N | 0.347 | neutral | None | None | None | None | I |
| A/K | 0.9686 | likely_pathogenic | 0.9724 | pathogenic | -0.809 | Destabilizing | 0.7 | D | 0.399 | neutral | None | None | None | None | I |
| A/L | 0.274 | likely_benign | 0.2993 | benign | -0.292 | Destabilizing | 0.25 | N | 0.367 | neutral | None | None | None | None | I |
| A/M | 0.4129 | ambiguous | 0.4723 | ambiguous | -0.414 | Destabilizing | 0.947 | D | 0.425 | neutral | None | None | None | None | I |
| A/N | 0.656 | likely_pathogenic | 0.6758 | pathogenic | -0.452 | Destabilizing | 0.7 | D | 0.531 | neutral | None | None | None | None | I |
| A/P | 0.9055 | likely_pathogenic | 0.8778 | pathogenic | -0.316 | Destabilizing | 0.781 | D | 0.413 | neutral | N | 0.509534032 | None | None | I |
| A/Q | 0.7973 | likely_pathogenic | 0.797 | pathogenic | -0.667 | Destabilizing | 0.826 | D | 0.413 | neutral | None | None | None | None | I |
| A/R | 0.9269 | likely_pathogenic | 0.926 | pathogenic | -0.385 | Destabilizing | 0.7 | D | 0.403 | neutral | None | None | None | None | I |
| A/S | 0.1717 | likely_benign | 0.1775 | benign | -0.691 | Destabilizing | 0.201 | N | 0.387 | neutral | N | 0.424952565 | None | None | I |
| A/T | 0.1664 | likely_benign | 0.2268 | benign | -0.703 | Destabilizing | 0.002 | N | 0.263 | neutral | N | 0.457835775 | None | None | I |
| A/V | 0.2319 | likely_benign | 0.2552 | benign | -0.316 | Destabilizing | 0.002 | N | 0.277 | neutral | N | 0.448024213 | None | None | I |
| A/W | 0.9698 | likely_pathogenic | 0.9631 | pathogenic | -1.05 | Destabilizing | 0.982 | D | 0.689 | prob.neutral | None | None | None | None | I |
| A/Y | 0.8956 | likely_pathogenic | 0.8869 | pathogenic | -0.677 | Destabilizing | 0.826 | D | 0.544 | 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.