Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22736 | 68431;68432;68433 | chr2:178578824;178578823;178578822 | chr2:179443551;179443550;179443549 |
| N2AB | 21095 | 63508;63509;63510 | chr2:178578824;178578823;178578822 | chr2:179443551;179443550;179443549 |
| N2A | 20168 | 60727;60728;60729 | chr2:178578824;178578823;178578822 | chr2:179443551;179443550;179443549 |
| N2B | 13671 | 41236;41237;41238 | chr2:178578824;178578823;178578822 | chr2:179443551;179443550;179443549 |
| Novex-1 | 13796 | 41611;41612;41613 | chr2:178578824;178578823;178578822 | chr2:179443551;179443550;179443549 |
| Novex-2 | 13863 | 41812;41813;41814 | chr2:178578824;178578823;178578822 | chr2:179443551;179443550;179443549 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1398519394  |
-1.486 | 0.469 | N | 0.436 | 0.23 | 0.518585293439 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66834E-04 |
| V/A | rs1398519394 |
-1.486 | 0.469 | N | 0.436 | 0.23 | 0.518585293439 | gnomAD-4.0.0 | 1.59809E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.0338E-05 |
| V/G | rs1398519394 |
None | 0.938 | N | 0.709 | 0.459 | 0.737181652176 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/G | rs1398519394 |
None | 0.938 | N | 0.709 | 0.459 | 0.737181652176 | gnomAD-4.0.0 | 6.57774E-06 | None | None | None | None | N | None | 2.41289E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2272 | likely_benign | 0.1717 | benign | -1.079 | Destabilizing | 0.469 | N | 0.436 | neutral | N | 0.502834559 | None | None | N |
| V/C | 0.6794 | likely_pathogenic | 0.6103 | pathogenic | -0.848 | Destabilizing | 0.996 | D | 0.646 | neutral | None | None | None | None | N |
| V/D | 0.6304 | likely_pathogenic | 0.4886 | ambiguous | -0.773 | Destabilizing | 0.979 | D | 0.772 | deleterious | N | 0.474794917 | None | None | N |
| V/E | 0.3919 | ambiguous | 0.3085 | benign | -0.814 | Destabilizing | 0.984 | D | 0.669 | prob.neutral | None | None | None | None | N |
| V/F | 0.2031 | likely_benign | 0.1484 | benign | -0.867 | Destabilizing | 0.883 | D | 0.629 | neutral | N | 0.491060127 | None | None | N |
| V/G | 0.4444 | ambiguous | 0.328 | benign | -1.341 | Destabilizing | 0.938 | D | 0.709 | prob.delet. | N | 0.487076275 | None | None | N |
| V/H | 0.5943 | likely_pathogenic | 0.489 | ambiguous | -0.816 | Destabilizing | 0.996 | D | 0.818 | deleterious | None | None | None | None | N |
| V/I | 0.0657 | likely_benign | 0.0641 | benign | -0.489 | Destabilizing | 0.003 | N | 0.1 | neutral | N | 0.439804588 | None | None | N |
| V/K | 0.3893 | ambiguous | 0.2982 | benign | -0.966 | Destabilizing | 0.953 | D | 0.676 | prob.neutral | None | None | None | None | N |
| V/L | 0.1343 | likely_benign | 0.1211 | benign | -0.489 | Destabilizing | 0.003 | N | 0.172 | neutral | N | 0.455080684 | None | None | N |
| V/M | 0.1288 | likely_benign | 0.1031 | benign | -0.443 | Destabilizing | 0.909 | D | 0.592 | neutral | None | None | None | None | N |
| V/N | 0.4025 | ambiguous | 0.3159 | benign | -0.744 | Destabilizing | 0.984 | D | 0.783 | deleterious | None | None | None | None | N |
| V/P | 0.603 | likely_pathogenic | 0.5232 | ambiguous | -0.649 | Destabilizing | 0.984 | D | 0.716 | prob.delet. | None | None | None | None | N |
| V/Q | 0.3636 | ambiguous | 0.2952 | benign | -0.937 | Destabilizing | 0.984 | D | 0.748 | deleterious | None | None | None | None | N |
| V/R | 0.3457 | ambiguous | 0.2639 | benign | -0.418 | Destabilizing | 0.984 | D | 0.781 | deleterious | None | None | None | None | N |
| V/S | 0.3139 | likely_benign | 0.2394 | benign | -1.225 | Destabilizing | 0.953 | D | 0.599 | neutral | None | None | None | None | N |
| V/T | 0.1434 | likely_benign | 0.1172 | benign | -1.156 | Destabilizing | 0.74 | D | 0.506 | neutral | None | None | None | None | N |
| V/W | 0.8014 | likely_pathogenic | 0.6907 | pathogenic | -0.999 | Destabilizing | 0.996 | D | 0.797 | deleterious | None | None | None | None | N |
| V/Y | 0.5632 | ambiguous | 0.4505 | ambiguous | -0.715 | Destabilizing | 0.953 | D | 0.671 | 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.