Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27581 | 82966;82967;82968 | chr2:178563391;178563390;178563389 | chr2:179428118;179428117;179428116 |
| N2AB | 25940 | 78043;78044;78045 | chr2:178563391;178563390;178563389 | chr2:179428118;179428117;179428116 |
| N2A | 25013 | 75262;75263;75264 | chr2:178563391;178563390;178563389 | chr2:179428118;179428117;179428116 |
| N2B | 18516 | 55771;55772;55773 | chr2:178563391;178563390;178563389 | chr2:179428118;179428117;179428116 |
| Novex-1 | 18641 | 56146;56147;56148 | chr2:178563391;178563390;178563389 | chr2:179428118;179428117;179428116 |
| Novex-2 | 18708 | 56347;56348;56349 | chr2:178563391;178563390;178563389 | chr2:179428118;179428117;179428116 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/Y | rs1471458270  |
-0.06 | 1.0 | N | 0.667 | 0.426 | 0.659863245131 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| D/Y | rs1471458270 |
-0.06 | 1.0 | N | 0.667 | 0.426 | 0.659863245131 | gnomAD-4.0.0 | 1.36853E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.799E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7551 | likely_pathogenic | 0.5675 | pathogenic | -0.397 | Destabilizing | 0.989 | D | 0.549 | neutral | N | 0.470203469 | None | None | N |
| D/C | 0.972 | likely_pathogenic | 0.9428 | pathogenic | 0.231 | Stabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| D/E | 0.6979 | likely_pathogenic | 0.5378 | ambiguous | -0.457 | Destabilizing | 0.989 | D | 0.415 | neutral | N | 0.490100122 | None | None | N |
| D/F | 0.9632 | likely_pathogenic | 0.9304 | pathogenic | -0.687 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| D/G | 0.6682 | likely_pathogenic | 0.5 | ambiguous | -0.583 | Destabilizing | 0.217 | N | 0.261 | neutral | N | 0.483396653 | None | None | N |
| D/H | 0.8886 | likely_pathogenic | 0.7839 | pathogenic | -0.871 | Destabilizing | 1.0 | D | 0.641 | neutral | N | 0.496780875 | None | None | N |
| D/I | 0.967 | likely_pathogenic | 0.9317 | pathogenic | 0.044 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| D/K | 0.9512 | likely_pathogenic | 0.8928 | pathogenic | 0.322 | Stabilizing | 0.998 | D | 0.647 | neutral | None | None | None | None | N |
| D/L | 0.9454 | likely_pathogenic | 0.891 | pathogenic | 0.044 | Stabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | N |
| D/M | 0.9795 | likely_pathogenic | 0.9563 | pathogenic | 0.473 | Stabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | N |
| D/N | 0.3512 | ambiguous | 0.2374 | benign | 0.121 | Stabilizing | 0.733 | D | 0.202 | neutral | N | 0.52015367 | None | None | N |
| D/P | 0.9974 | likely_pathogenic | 0.9951 | pathogenic | -0.081 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| D/Q | 0.9106 | likely_pathogenic | 0.816 | pathogenic | 0.113 | Stabilizing | 0.999 | D | 0.601 | neutral | None | None | None | None | N |
| D/R | 0.9399 | likely_pathogenic | 0.8797 | pathogenic | 0.212 | Stabilizing | 0.999 | D | 0.666 | neutral | None | None | None | None | N |
| D/S | 0.5323 | ambiguous | 0.3606 | ambiguous | 0.013 | Stabilizing | 0.992 | D | 0.444 | neutral | None | None | None | None | N |
| D/T | 0.8695 | likely_pathogenic | 0.7605 | pathogenic | 0.16 | Stabilizing | 0.998 | D | 0.638 | neutral | None | None | None | None | N |
| D/V | 0.8972 | likely_pathogenic | 0.8079 | pathogenic | -0.081 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | N | 0.491563408 | None | None | N |
| D/W | 0.9944 | likely_pathogenic | 0.9901 | pathogenic | -0.641 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| D/Y | 0.8165 | likely_pathogenic | 0.7002 | pathogenic | -0.465 | Destabilizing | 1.0 | D | 0.667 | neutral | N | 0.490526678 | 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.