Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35195 | 105808;105809;105810 | chr2:178531032;178531031;178531030 | chr2:179395759;179395758;179395757 |
| N2AB | 33554 | 100885;100886;100887 | chr2:178531032;178531031;178531030 | chr2:179395759;179395758;179395757 |
| N2A | 32627 | 98104;98105;98106 | chr2:178531032;178531031;178531030 | chr2:179395759;179395758;179395757 |
| N2B | 26130 | 78613;78614;78615 | chr2:178531032;178531031;178531030 | chr2:179395759;179395758;179395757 |
| Novex-1 | 26255 | 78988;78989;78990 | chr2:178531032;178531031;178531030 | chr2:179395759;179395758;179395757 |
| Novex-2 | 26322 | 79189;79190;79191 | chr2:178531032;178531031;178531030 | chr2:179395759;179395758;179395757 |
| 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/N | rs752458663  |
-0.179 | 1.0 | D | 0.803 | 0.705 | 0.661029647469 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.86E-06 | 3.30579E-04 |
| D/N | rs752458663 |
-0.179 | 1.0 | D | 0.803 | 0.705 | 0.661029647469 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs752458663 |
-0.179 | 1.0 | D | 0.803 | 0.705 | 0.661029647469 | gnomAD-4.0.0 | 1.30129E-05 | None | None | None | None | N | None | 0 | 1.66656E-05 | None | 0 | 0 | None | 1.56304E-05 | 3.28731E-04 | 1.35606E-05 | 0 | 1.60097E-05 |
| D/V | None | None | 1.0 | D | 0.879 | 0.86 | 0.850925399445 | gnomAD-4.0.0 | 4.80129E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25001E-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 | 0.7912 | likely_pathogenic | 0.9242 | pathogenic | 0.027 | Stabilizing | 1.0 | D | 0.868 | deleterious | D | 0.634121574 | None | None | N |
| D/C | 0.9597 | likely_pathogenic | 0.9814 | pathogenic | 0.022 | Stabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| D/E | 0.6369 | likely_pathogenic | 0.7889 | pathogenic | -0.809 | Destabilizing | 0.999 | D | 0.58 | neutral | D | 0.611551601 | None | None | N |
| D/F | 0.9621 | likely_pathogenic | 0.9869 | pathogenic | 0.606 | Stabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| D/G | 0.8524 | likely_pathogenic | 0.9425 | pathogenic | -0.42 | Destabilizing | 1.0 | D | 0.824 | deleterious | D | 0.65034274 | None | None | N |
| D/H | 0.7863 | likely_pathogenic | 0.911 | pathogenic | 0.129 | Stabilizing | 1.0 | D | 0.88 | deleterious | D | 0.592039052 | None | None | N |
| D/I | 0.9637 | likely_pathogenic | 0.987 | pathogenic | 1.225 | Stabilizing | 1.0 | D | 0.888 | deleterious | None | None | None | None | N |
| D/K | 0.9452 | likely_pathogenic | 0.979 | pathogenic | -0.306 | Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | N |
| D/L | 0.9441 | likely_pathogenic | 0.9775 | pathogenic | 1.225 | Stabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| D/M | 0.9727 | likely_pathogenic | 0.9896 | pathogenic | 1.677 | Stabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| D/N | 0.4786 | ambiguous | 0.7207 | pathogenic | -0.978 | Destabilizing | 1.0 | D | 0.803 | deleterious | D | 0.616487779 | None | None | N |
| D/P | 0.9944 | likely_pathogenic | 0.9977 | pathogenic | 0.855 | Stabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| D/Q | 0.8881 | likely_pathogenic | 0.9572 | pathogenic | -0.662 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| D/R | 0.9504 | likely_pathogenic | 0.9791 | pathogenic | -0.234 | Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| D/S | 0.5898 | likely_pathogenic | 0.8276 | pathogenic | -1.241 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| D/T | 0.897 | likely_pathogenic | 0.9645 | pathogenic | -0.849 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| D/V | 0.8867 | likely_pathogenic | 0.9547 | pathogenic | 0.855 | Stabilizing | 1.0 | D | 0.879 | deleterious | D | 0.650746348 | None | None | N |
| D/W | 0.9899 | likely_pathogenic | 0.9957 | pathogenic | 0.642 | Stabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| D/Y | 0.7644 | likely_pathogenic | 0.9059 | pathogenic | 0.822 | Stabilizing | 1.0 | D | 0.9 | deleterious | D | 0.666563905 | 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.