Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7435 | 22528;22529;22530 | chr2:178722484;178722483;178722482 | chr2:179587211;179587210;179587209 |
| N2AB | 7118 | 21577;21578;21579 | chr2:178722484;178722483;178722482 | chr2:179587211;179587210;179587209 |
| N2A | 6191 | 18796;18797;18798 | chr2:178722484;178722483;178722482 | chr2:179587211;179587210;179587209 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 | rs540312596  |
-0.262 | 0.502 | N | 0.412 | 0.244 | 0.712169444321 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| P/L | rs540312596 |
-0.262 | 0.502 | N | 0.412 | 0.244 | 0.712169444321 | 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 |
| P/L | rs540312596 |
-0.262 | 0.502 | N | 0.412 | 0.244 | 0.712169444321 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| P/S | rs375037712 |
-0.912 | 0.978 | N | 0.495 | 0.287 | None | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.7E-05 | 0 |
| P/S | rs375037712 |
-0.912 | 0.978 | N | 0.495 | 0.287 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| P/S | rs375037712 |
-0.912 | 0.978 | N | 0.495 | 0.287 | None | gnomAD-4.0.0 | 3.96699E-05 | None | None | None | None | N | None | 5.34259E-05 | 0 | None | 0 | 0 | None | 1.56226E-05 | 0 | 4.74759E-05 | 0 | 4.80477E-05 |
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 | 0.1161 | likely_benign | 0.1102 | benign | -1.131 | Destabilizing | 0.26 | N | 0.299 | neutral | N | 0.514950999 | None | None | N |
| P/C | 0.8122 | likely_pathogenic | 0.7659 | pathogenic | -0.818 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| P/D | 0.6392 | likely_pathogenic | 0.5971 | pathogenic | -0.7 | Destabilizing | 0.984 | D | 0.571 | neutral | None | None | None | None | N |
| P/E | 0.4442 | ambiguous | 0.425 | ambiguous | -0.743 | Destabilizing | 0.99 | D | 0.534 | neutral | None | None | None | None | N |
| P/F | 0.7385 | likely_pathogenic | 0.7209 | pathogenic | -0.917 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | None | None | None | None | N |
| P/G | 0.4672 | ambiguous | 0.4315 | ambiguous | -1.389 | Destabilizing | 0.989 | D | 0.499 | neutral | None | None | None | None | N |
| P/H | 0.3983 | ambiguous | 0.3887 | ambiguous | -0.796 | Destabilizing | 1.0 | D | 0.649 | neutral | N | 0.495403247 | None | None | N |
| P/I | 0.6502 | likely_pathogenic | 0.6209 | pathogenic | -0.553 | Destabilizing | 0.93 | D | 0.44 | neutral | None | None | None | None | N |
| P/K | 0.6189 | likely_pathogenic | 0.6033 | pathogenic | -0.897 | Destabilizing | 1.0 | D | 0.535 | neutral | None | None | None | None | N |
| P/L | 0.2403 | likely_benign | 0.2452 | benign | -0.553 | Destabilizing | 0.502 | D | 0.412 | neutral | N | 0.487654566 | None | None | N |
| P/M | 0.56 | ambiguous | 0.5448 | ambiguous | -0.437 | Destabilizing | 0.998 | D | 0.655 | neutral | None | None | None | None | N |
| P/N | 0.5292 | ambiguous | 0.4983 | ambiguous | -0.663 | Destabilizing | 0.999 | D | 0.648 | neutral | None | None | None | None | N |
| P/Q | 0.2996 | likely_benign | 0.3021 | benign | -0.877 | Destabilizing | 1.0 | D | 0.593 | neutral | None | None | None | None | N |
| P/R | 0.3852 | ambiguous | 0.3885 | ambiguous | -0.326 | Destabilizing | 1.0 | D | 0.651 | neutral | N | 0.512412126 | None | None | N |
| P/S | 0.1801 | likely_benign | 0.1744 | benign | -1.184 | Destabilizing | 0.978 | D | 0.495 | neutral | N | 0.43379384 | None | None | N |
| P/T | 0.1974 | likely_benign | 0.1902 | benign | -1.121 | Destabilizing | 0.976 | D | 0.487 | neutral | N | 0.490033912 | None | None | N |
| P/V | 0.4372 | ambiguous | 0.426 | ambiguous | -0.709 | Destabilizing | 0.974 | D | 0.521 | neutral | None | None | None | None | N |
| P/W | 0.836 | likely_pathogenic | 0.8296 | pathogenic | -1.023 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| P/Y | 0.7203 | likely_pathogenic | 0.7037 | pathogenic | -0.748 | Destabilizing | 1.0 | D | 0.683 | 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.