Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23397 | 70414;70415;70416 | chr2:178575943;178575942;178575941 | chr2:179440670;179440669;179440668 |
| N2AB | 21756 | 65491;65492;65493 | chr2:178575943;178575942;178575941 | chr2:179440670;179440669;179440668 |
| N2A | 20829 | 62710;62711;62712 | chr2:178575943;178575942;178575941 | chr2:179440670;179440669;179440668 |
| N2B | 14332 | 43219;43220;43221 | chr2:178575943;178575942;178575941 | chr2:179440670;179440669;179440668 |
| Novex-1 | 14457 | 43594;43595;43596 | chr2:178575943;178575942;178575941 | chr2:179440670;179440669;179440668 |
| Novex-2 | 14524 | 43795;43796;43797 | chr2:178575943;178575942;178575941 | chr2:179440670;179440669;179440668 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/C | rs1409813527  |
None | 1.0 | N | 0.65 | 0.34 | 0.748869319524 | gnomAD-4.0.0 | 7.53357E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.90477E-06 | 0 | 0 |
| F/L | rs1445569607 |
-1.258 | 0.91 | N | 0.389 | 0.357 | 0.416328079214 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| F/L | rs1445569607 |
-1.258 | 0.91 | N | 0.389 | 0.357 | 0.416328079214 | gnomAD-4.0.0 | 1.59584E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87086E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.9122 | likely_pathogenic | 0.9374 | pathogenic | -2.456 | Highly Destabilizing | 0.985 | D | 0.561 | neutral | None | None | None | None | N |
| F/C | 0.677 | likely_pathogenic | 0.755 | pathogenic | -1.466 | Destabilizing | 1.0 | D | 0.65 | neutral | N | 0.460119224 | None | None | N |
| F/D | 0.9587 | likely_pathogenic | 0.9763 | pathogenic | -1.65 | Destabilizing | 0.999 | D | 0.682 | prob.neutral | None | None | None | None | N |
| F/E | 0.9785 | likely_pathogenic | 0.9859 | pathogenic | -1.509 | Destabilizing | 0.999 | D | 0.648 | neutral | None | None | None | None | N |
| F/G | 0.9586 | likely_pathogenic | 0.9716 | pathogenic | -2.851 | Highly Destabilizing | 0.999 | D | 0.622 | neutral | None | None | None | None | N |
| F/H | 0.7495 | likely_pathogenic | 0.8162 | pathogenic | -1.199 | Destabilizing | 0.991 | D | 0.611 | neutral | None | None | None | None | N |
| F/I | 0.8313 | likely_pathogenic | 0.8979 | pathogenic | -1.224 | Destabilizing | 0.98 | D | 0.423 | neutral | N | 0.448880723 | None | None | N |
| F/K | 0.9774 | likely_pathogenic | 0.9865 | pathogenic | -1.447 | Destabilizing | 0.996 | D | 0.655 | neutral | None | None | None | None | N |
| F/L | 0.9839 | likely_pathogenic | 0.9901 | pathogenic | -1.224 | Destabilizing | 0.91 | D | 0.389 | neutral | N | 0.415885657 | None | None | N |
| F/M | 0.8614 | likely_pathogenic | 0.909 | pathogenic | -0.94 | Destabilizing | 0.999 | D | 0.489 | neutral | None | None | None | None | N |
| F/N | 0.872 | likely_pathogenic | 0.9185 | pathogenic | -1.621 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| F/P | 0.9994 | likely_pathogenic | 0.9996 | pathogenic | -1.635 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | N |
| F/Q | 0.9485 | likely_pathogenic | 0.9632 | pathogenic | -1.657 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | N |
| F/R | 0.9448 | likely_pathogenic | 0.9623 | pathogenic | -0.851 | Destabilizing | 0.996 | D | 0.689 | prob.neutral | None | None | None | None | N |
| F/S | 0.7918 | likely_pathogenic | 0.8473 | pathogenic | -2.453 | Highly Destabilizing | 0.994 | D | 0.603 | neutral | N | 0.407938177 | None | None | N |
| F/T | 0.9061 | likely_pathogenic | 0.9463 | pathogenic | -2.209 | Highly Destabilizing | 0.996 | D | 0.605 | neutral | None | None | None | None | N |
| F/V | 0.7564 | likely_pathogenic | 0.8391 | pathogenic | -1.635 | Destabilizing | 0.961 | D | 0.479 | neutral | N | 0.454403973 | None | None | N |
| F/W | 0.7004 | likely_pathogenic | 0.7515 | pathogenic | -0.391 | Destabilizing | 0.996 | D | 0.499 | neutral | None | None | None | None | N |
| F/Y | 0.1059 | likely_benign | 0.1204 | benign | -0.643 | Destabilizing | 0.044 | N | 0.157 | neutral | N | 0.394048947 | 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.