Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33716 | 101371;101372;101373 | chr2:178535469;178535468;178535467 | chr2:179400196;179400195;179400194 |
| N2AB | 32075 | 96448;96449;96450 | chr2:178535469;178535468;178535467 | chr2:179400196;179400195;179400194 |
| N2A | 31148 | 93667;93668;93669 | chr2:178535469;178535468;178535467 | chr2:179400196;179400195;179400194 |
| N2B | 24651 | 74176;74177;74178 | chr2:178535469;178535468;178535467 | chr2:179400196;179400195;179400194 |
| Novex-1 | 24776 | 74551;74552;74553 | chr2:178535469;178535468;178535467 | chr2:179400196;179400195;179400194 |
| Novex-2 | 24843 | 74752;74753;74754 | chr2:178535469;178535468;178535467 | chr2:179400196;179400195;179400194 |
| 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/G | rs1300576084  |
-0.092 | 0.905 | N | 0.617 | 0.417 | 0.409262747536 | 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 |
| D/G | rs1300576084 |
-0.092 | 0.905 | N | 0.617 | 0.417 | 0.409262747536 | gnomAD-4.0.0 | 1.59115E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85794E-06 | 0 | 0 |
| D/N | None | None | 0.078 | N | 0.277 | 0.252 | 0.263140351381 | gnomAD-4.0.0 | 1.5912E-06 | None | None | None | None | N | None | 0 | 2.28728E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.6595 | likely_pathogenic | 0.4945 | ambiguous | -0.189 | Destabilizing | 0.989 | D | 0.629 | neutral | N | 0.484497333 | None | None | N |
| D/C | 0.9246 | likely_pathogenic | 0.8809 | pathogenic | 0.223 | Stabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | N |
| D/E | 0.7725 | likely_pathogenic | 0.6427 | pathogenic | -0.651 | Destabilizing | 0.747 | D | 0.448 | neutral | N | 0.475912505 | None | None | N |
| D/F | 0.9535 | likely_pathogenic | 0.9095 | pathogenic | -0.589 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | N |
| D/G | 0.6399 | likely_pathogenic | 0.4867 | ambiguous | -0.418 | Destabilizing | 0.905 | D | 0.617 | neutral | N | 0.495791187 | None | None | N |
| D/H | 0.7879 | likely_pathogenic | 0.6725 | pathogenic | -0.948 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | N | 0.493473782 | None | None | N |
| D/I | 0.9209 | likely_pathogenic | 0.838 | pathogenic | 0.371 | Stabilizing | 0.999 | D | 0.666 | neutral | None | None | None | None | N |
| D/K | 0.9198 | likely_pathogenic | 0.8275 | pathogenic | 0.183 | Stabilizing | 0.998 | D | 0.647 | neutral | None | None | None | None | N |
| D/L | 0.8994 | likely_pathogenic | 0.8205 | pathogenic | 0.371 | Stabilizing | 0.999 | D | 0.654 | neutral | None | None | None | None | N |
| D/M | 0.9683 | likely_pathogenic | 0.9356 | pathogenic | 0.835 | Stabilizing | 1.0 | D | 0.632 | neutral | None | None | None | None | N |
| D/N | 0.1574 | likely_benign | 0.1263 | benign | -0.066 | Destabilizing | 0.078 | N | 0.277 | neutral | N | 0.462596594 | None | None | N |
| D/P | 0.924 | likely_pathogenic | 0.8585 | pathogenic | 0.209 | Stabilizing | 0.982 | D | 0.715 | prob.delet. | None | None | None | None | N |
| D/Q | 0.9098 | likely_pathogenic | 0.8156 | pathogenic | -0.02 | Destabilizing | 0.994 | D | 0.73 | prob.delet. | None | None | None | None | N |
| D/R | 0.9217 | likely_pathogenic | 0.8239 | pathogenic | 0.008 | Stabilizing | 0.998 | D | 0.672 | neutral | None | None | None | None | N |
| D/S | 0.3337 | likely_benign | 0.2392 | benign | -0.18 | Destabilizing | 0.946 | D | 0.625 | neutral | None | None | None | None | N |
| D/T | 0.6312 | likely_pathogenic | 0.5155 | ambiguous | 0.006 | Stabilizing | 0.982 | D | 0.647 | neutral | None | None | None | None | N |
| D/V | 0.8173 | likely_pathogenic | 0.6792 | pathogenic | 0.209 | Stabilizing | 0.992 | D | 0.653 | neutral | N | 0.501867573 | None | None | N |
| D/W | 0.9896 | likely_pathogenic | 0.9823 | pathogenic | -0.647 | Destabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | N |
| D/Y | 0.7263 | likely_pathogenic | 0.566 | pathogenic | -0.393 | Destabilizing | 1.0 | D | 0.639 | neutral | D | 0.531835112 | 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.