Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19277 | 58054;58055;58056 | chr2:178595525;178595524;178595523 | chr2:179460252;179460251;179460250 |
| N2AB | 17636 | 53131;53132;53133 | chr2:178595525;178595524;178595523 | chr2:179460252;179460251;179460250 |
| N2A | 16709 | 50350;50351;50352 | chr2:178595525;178595524;178595523 | chr2:179460252;179460251;179460250 |
| N2B | 10212 | 30859;30860;30861 | chr2:178595525;178595524;178595523 | chr2:179460252;179460251;179460250 |
| Novex-1 | 10337 | 31234;31235;31236 | chr2:178595525;178595524;178595523 | chr2:179460252;179460251;179460250 |
| Novex-2 | 10404 | 31435;31436;31437 | chr2:178595525;178595524;178595523 | chr2:179460252;179460251;179460250 |
| 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/I | rs1398372843  |
-0.044 | None | N | 0.114 | 0.075 | 0.422160833541 | gnomAD-2.1.1 | 5.91E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.47E-05 | 0 |
| V/I | rs1398372843 |
-0.044 | None | N | 0.114 | 0.075 | 0.422160833541 | gnomAD-4.0.0 | 7.11096E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.23996E-07 | 0 | 0 |
| V/L | None | None | None | N | 0.103 | 0.072 | 0.347879110917 | gnomAD-4.0.0 | 7.11096E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.23996E-07 | 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 | 0.209 | likely_benign | 0.2479 | benign | -0.879 | Destabilizing | 0.025 | N | 0.427 | neutral | N | 0.521375539 | None | None | N |
| V/C | 0.6537 | likely_pathogenic | 0.7003 | pathogenic | -0.809 | Destabilizing | 0.869 | D | 0.528 | neutral | None | None | None | None | N |
| V/D | 0.3211 | likely_benign | 0.427 | ambiguous | -0.341 | Destabilizing | 0.303 | N | 0.684 | prob.delet. | N | 0.502262874 | None | None | N |
| V/E | 0.2475 | likely_benign | 0.3203 | benign | -0.361 | Destabilizing | 0.366 | N | 0.617 | neutral | None | None | None | None | N |
| V/F | 0.1663 | likely_benign | 0.1964 | benign | -0.605 | Destabilizing | 0.177 | N | 0.597 | neutral | D | 0.533286044 | None | None | N |
| V/G | 0.2809 | likely_benign | 0.3336 | benign | -1.145 | Destabilizing | 0.303 | N | 0.655 | prob.neutral | N | 0.501755895 | None | None | N |
| V/H | 0.4565 | ambiguous | 0.5519 | ambiguous | -0.523 | Destabilizing | 0.869 | D | 0.674 | prob.neutral | None | None | None | None | N |
| V/I | 0.0713 | likely_benign | 0.0737 | benign | -0.277 | Destabilizing | None | N | 0.114 | neutral | N | 0.491572707 | None | None | N |
| V/K | 0.3472 | ambiguous | 0.4393 | ambiguous | -0.762 | Destabilizing | 0.366 | N | 0.602 | neutral | None | None | None | None | N |
| V/L | 0.1093 | likely_benign | 0.1323 | benign | -0.277 | Destabilizing | None | N | 0.103 | neutral | N | 0.463655387 | None | None | N |
| V/M | 0.1307 | likely_benign | 0.1451 | benign | -0.403 | Destabilizing | 0.221 | N | 0.537 | neutral | None | None | None | None | N |
| V/N | 0.2285 | likely_benign | 0.2816 | benign | -0.623 | Destabilizing | 0.366 | N | 0.717 | prob.delet. | None | None | None | None | N |
| V/P | 0.4376 | ambiguous | 0.4771 | ambiguous | -0.441 | Destabilizing | 0.637 | D | 0.665 | prob.neutral | None | None | None | None | N |
| V/Q | 0.2936 | likely_benign | 0.3454 | ambiguous | -0.746 | Destabilizing | 0.637 | D | 0.629 | neutral | None | None | None | None | N |
| V/R | 0.3364 | likely_benign | 0.4245 | ambiguous | -0.294 | Destabilizing | 0.366 | N | 0.715 | prob.delet. | None | None | None | None | N |
| V/S | 0.234 | likely_benign | 0.274 | benign | -1.147 | Destabilizing | 0.039 | N | 0.598 | neutral | None | None | None | None | N |
| V/T | 0.1575 | likely_benign | 0.1805 | benign | -1.046 | Destabilizing | 0.001 | N | 0.257 | neutral | None | None | None | None | N |
| V/W | 0.7518 | likely_pathogenic | 0.8176 | pathogenic | -0.743 | Destabilizing | 0.869 | D | 0.715 | prob.delet. | None | None | None | None | N |
| V/Y | 0.4691 | ambiguous | 0.5484 | ambiguous | -0.445 | Destabilizing | 0.366 | N | 0.602 | 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.