Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28789 | 86590;86591;86592 | chr2:178559767;178559766;178559765 | chr2:179424494;179424493;179424492 |
| N2AB | 27148 | 81667;81668;81669 | chr2:178559767;178559766;178559765 | chr2:179424494;179424493;179424492 |
| N2A | 26221 | 78886;78887;78888 | chr2:178559767;178559766;178559765 | chr2:179424494;179424493;179424492 |
| N2B | 19724 | 59395;59396;59397 | chr2:178559767;178559766;178559765 | chr2:179424494;179424493;179424492 |
| Novex-1 | 19849 | 59770;59771;59772 | chr2:178559767;178559766;178559765 | chr2:179424494;179424493;179424492 |
| Novex-2 | 19916 | 59971;59972;59973 | chr2:178559767;178559766;178559765 | chr2:179424494;179424493;179424492 |
| 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 | 0.09 | N | 0.593 | 0.104 | 0.126345400529 | gnomAD-4.0.0 | 6.89843E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.04331E-07 | 0 | 0 |
| S/N | rs1465190956  |
None | 0.001 | N | 0.241 | 0.072 | 0.104622674875 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 1.30941E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | rs1465190956 |
None | 0.001 | N | 0.241 | 0.072 | 0.104622674875 | gnomAD-4.0.0 | 5.2079E-06 | None | None | None | None | N | None | 1.69843E-05 | 3.42983E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 2.889E-05 |
| S/R | rs774223958 |
-0.352 | 0.627 | N | 0.715 | 0.145 | 0.112648838833 | gnomAD-2.1.1 | 2.95E-05 | None | None | None | None | N | None | 0 | 2.88E-05 | None | 0 | 0 | None | 0 | None | 2.13895E-04 | 1.61E-05 | 0 |
| S/R | rs774223958 |
-0.352 | 0.627 | N | 0.715 | 0.145 | 0.112648838833 | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 6.59506E-04 | 0 | 1.47E-05 | 0 | 0 |
| S/R | rs774223958 |
-0.352 | 0.627 | N | 0.715 | 0.145 | 0.112648838833 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-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 | 0.0973 | likely_benign | 0.094 | benign | -0.653 | Destabilizing | 0.008 | N | 0.268 | neutral | None | None | None | None | N |
| S/C | 0.0916 | likely_benign | 0.0973 | benign | -0.329 | Destabilizing | 0.975 | D | 0.668 | neutral | N | 0.473213711 | None | None | N |
| S/D | 0.3209 | likely_benign | 0.3365 | benign | 0.405 | Stabilizing | 0.241 | N | 0.604 | neutral | None | None | None | None | N |
| S/E | 0.366 | ambiguous | 0.3599 | ambiguous | 0.452 | Stabilizing | 0.388 | N | 0.603 | neutral | None | None | None | None | N |
| S/F | 0.2015 | likely_benign | 0.1839 | benign | -0.907 | Destabilizing | 0.932 | D | 0.725 | prob.delet. | None | None | None | None | N |
| S/G | 0.0928 | likely_benign | 0.0975 | benign | -0.918 | Destabilizing | 0.09 | N | 0.593 | neutral | N | 0.507290655 | None | None | N |
| S/H | 0.2289 | likely_benign | 0.2314 | benign | -1.175 | Destabilizing | 0.69 | D | 0.691 | prob.neutral | None | None | None | None | N |
| S/I | 0.1563 | likely_benign | 0.1576 | benign | -0.046 | Destabilizing | 0.627 | D | 0.71 | prob.delet. | N | 0.487664744 | None | None | N |
| S/K | 0.4693 | ambiguous | 0.4727 | ambiguous | -0.086 | Destabilizing | 0.241 | N | 0.607 | neutral | None | None | None | None | N |
| S/L | 0.1135 | likely_benign | 0.1029 | benign | -0.046 | Destabilizing | 0.388 | N | 0.694 | prob.neutral | None | None | None | None | N |
| S/M | 0.1458 | likely_benign | 0.1378 | benign | -0.083 | Destabilizing | 0.981 | D | 0.683 | prob.neutral | None | None | None | None | N |
| S/N | 0.0801 | likely_benign | 0.0878 | benign | -0.238 | Destabilizing | 0.001 | N | 0.241 | neutral | N | 0.465001315 | None | None | N |
| S/P | 0.9576 | likely_pathogenic | 0.9551 | pathogenic | -0.215 | Destabilizing | 0.818 | D | 0.713 | prob.delet. | None | None | None | None | N |
| S/Q | 0.3132 | likely_benign | 0.3126 | benign | -0.215 | Destabilizing | 0.69 | D | 0.678 | prob.neutral | None | None | None | None | N |
| S/R | 0.4119 | ambiguous | 0.4035 | ambiguous | -0.145 | Destabilizing | 0.627 | D | 0.715 | prob.delet. | N | 0.452186734 | None | None | N |
| S/T | 0.0725 | likely_benign | 0.0705 | benign | -0.266 | Destabilizing | 0.006 | N | 0.433 | neutral | N | 0.409838679 | None | None | N |
| S/V | 0.1596 | likely_benign | 0.1588 | benign | -0.215 | Destabilizing | 0.388 | N | 0.704 | prob.neutral | None | None | None | None | N |
| S/W | 0.3542 | ambiguous | 0.3342 | benign | -0.935 | Destabilizing | 0.981 | D | 0.732 | prob.delet. | None | None | None | None | N |
| S/Y | 0.1778 | likely_benign | 0.1723 | benign | -0.583 | Destabilizing | 0.932 | D | 0.727 | prob.delet. | 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.