Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23758 | 71497;71498;71499 | chr2:178574860;178574859;178574858 | chr2:179439587;179439586;179439585 |
| N2AB | 22117 | 66574;66575;66576 | chr2:178574860;178574859;178574858 | chr2:179439587;179439586;179439585 |
| N2A | 21190 | 63793;63794;63795 | chr2:178574860;178574859;178574858 | chr2:179439587;179439586;179439585 |
| N2B | 14693 | 44302;44303;44304 | chr2:178574860;178574859;178574858 | chr2:179439587;179439586;179439585 |
| Novex-1 | 14818 | 44677;44678;44679 | chr2:178574860;178574859;178574858 | chr2:179439587;179439586;179439585 |
| Novex-2 | 14885 | 44878;44879;44880 | chr2:178574860;178574859;178574858 | chr2:179439587;179439586;179439585 |
| 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/Q | rs374970767  |
-0.123 | 1.0 | N | 0.637 | 0.471 | None | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | I | None | 6.49E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/Q | rs374970767 |
-0.123 | 1.0 | N | 0.637 | 0.471 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/Q | rs374970767 |
-0.123 | 1.0 | N | 0.637 | 0.471 | None | gnomAD-4.0.0 | 3.84784E-06 | None | None | None | None | I | None | 5.07906E-05 | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1656 | likely_benign | 0.1188 | benign | -0.502 | Destabilizing | 1.0 | D | 0.638 | neutral | N | 0.505515078 | None | None | I |
| P/C | 0.8097 | likely_pathogenic | 0.7303 | pathogenic | -0.62 | Destabilizing | 1.0 | D | 0.646 | neutral | None | None | None | None | I |
| P/D | 0.8622 | likely_pathogenic | 0.8 | pathogenic | -0.193 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | I |
| P/E | 0.7164 | likely_pathogenic | 0.6314 | pathogenic | -0.303 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| P/F | 0.8678 | likely_pathogenic | 0.7931 | pathogenic | -0.71 | Destabilizing | 1.0 | D | 0.58 | neutral | None | None | None | None | I |
| P/G | 0.6511 | likely_pathogenic | 0.5185 | ambiguous | -0.642 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | I |
| P/H | 0.616 | likely_pathogenic | 0.4911 | ambiguous | -0.22 | Destabilizing | 1.0 | D | 0.593 | neutral | None | None | None | None | I |
| P/I | 0.6648 | likely_pathogenic | 0.5615 | ambiguous | -0.283 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | I |
| P/K | 0.8074 | likely_pathogenic | 0.7327 | pathogenic | -0.416 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | I |
| P/L | 0.3249 | likely_benign | 0.2529 | benign | -0.283 | Destabilizing | 1.0 | D | 0.666 | neutral | N | 0.499885201 | None | None | I |
| P/M | 0.5968 | likely_pathogenic | 0.4882 | ambiguous | -0.32 | Destabilizing | 1.0 | D | 0.596 | neutral | None | None | None | None | I |
| P/N | 0.6882 | likely_pathogenic | 0.5442 | ambiguous | -0.155 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | I |
| P/Q | 0.4436 | ambiguous | 0.3342 | benign | -0.387 | Destabilizing | 1.0 | D | 0.637 | neutral | N | 0.470714129 | None | None | I |
| P/R | 0.6898 | likely_pathogenic | 0.5996 | pathogenic | 0.086 | Stabilizing | 1.0 | D | 0.638 | neutral | N | 0.482830903 | None | None | I |
| P/S | 0.3498 | ambiguous | 0.2296 | benign | -0.542 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | N | 0.486336395 | None | None | I |
| P/T | 0.2917 | likely_benign | 0.2047 | benign | -0.546 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | N | 0.484121123 | None | None | I |
| P/V | 0.4784 | ambiguous | 0.3807 | ambiguous | -0.321 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| P/W | 0.9454 | likely_pathogenic | 0.9127 | pathogenic | -0.79 | Destabilizing | 1.0 | D | 0.654 | neutral | None | None | None | None | I |
| P/Y | 0.8556 | likely_pathogenic | 0.7822 | pathogenic | -0.487 | Destabilizing | 1.0 | D | 0.583 | 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.