Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20531 | 61816;61817;61818 | chr2:178590134;178590133;178590132 | chr2:179454861;179454860;179454859 |
| N2AB | 18890 | 56893;56894;56895 | chr2:178590134;178590133;178590132 | chr2:179454861;179454860;179454859 |
| N2A | 17963 | 54112;54113;54114 | chr2:178590134;178590133;178590132 | chr2:179454861;179454860;179454859 |
| N2B | 11466 | 34621;34622;34623 | chr2:178590134;178590133;178590132 | chr2:179454861;179454860;179454859 |
| Novex-1 | 11591 | 34996;34997;34998 | chr2:178590134;178590133;178590132 | chr2:179454861;179454860;179454859 |
| Novex-2 | 11658 | 35197;35198;35199 | chr2:178590134;178590133;178590132 | chr2:179454861;179454860;179454859 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs748005350  |
-0.702 | 0.975 | N | 0.463 | 0.37 | 0.557405679382 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 8.91E-06 | 0 |
| R/C | rs748005350 |
-0.702 | 0.975 | N | 0.463 | 0.37 | 0.557405679382 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs748005350 |
-0.702 | 0.975 | N | 0.463 | 0.37 | 0.557405679382 | gnomAD-4.0.0 | 3.09969E-06 | None | None | None | None | N | None | 1.33611E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.5435E-06 | 0 | 1.60159E-05 |
| R/H | rs370887455 |
-1.428 | 0.006 | N | 0.158 | 0.219 | None | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 1.40766E-04 |
| R/H | rs370887455 |
-1.428 | 0.006 | N | 0.158 | 0.219 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs370887455 |
-1.428 | 0.006 | N | 0.158 | 0.219 | None | gnomAD-4.0.0 | 2.54167E-05 | None | None | None | None | N | None | 4.00727E-05 | 3.33622E-05 | None | 0 | 0 | None | 0 | 0 | 2.88262E-05 | 0 | 3.20338E-05 |
| R/L | rs370887455 |
0.191 | 0.001 | N | 0.187 | 0.3 | 0.406945738958 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| R/L | rs370887455 |
0.191 | 0.001 | N | 0.187 | 0.3 | 0.406945738958 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 0 |
| R/L | rs370887455 |
0.191 | 0.001 | N | 0.187 | 0.3 | 0.406945738958 | gnomAD-4.0.0 | 2.47968E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.39396E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2786 | likely_benign | 0.3702 | ambiguous | -0.902 | Destabilizing | 0.036 | N | 0.261 | neutral | None | None | None | None | N |
| R/C | 0.1602 | likely_benign | 0.2389 | benign | -0.865 | Destabilizing | 0.975 | D | 0.463 | neutral | N | 0.486268462 | None | None | N |
| R/D | 0.5147 | ambiguous | 0.6209 | pathogenic | -0.002 | Destabilizing | 0.08 | N | 0.42 | neutral | None | None | None | None | N |
| R/E | 0.3145 | likely_benign | 0.3957 | ambiguous | 0.156 | Stabilizing | 0.148 | N | 0.2 | neutral | None | None | None | None | N |
| R/F | 0.3876 | ambiguous | 0.4594 | ambiguous | -0.514 | Destabilizing | 0.174 | N | 0.564 | neutral | None | None | None | None | N |
| R/G | 0.2229 | likely_benign | 0.33 | benign | -1.251 | Destabilizing | 0.143 | N | 0.397 | neutral | N | 0.448403507 | None | None | N |
| R/H | 0.0974 | likely_benign | 0.1305 | benign | -1.434 | Destabilizing | 0.006 | N | 0.158 | neutral | N | 0.451097095 | None | None | N |
| R/I | 0.1879 | likely_benign | 0.2514 | benign | 0.054 | Stabilizing | 0.036 | N | 0.411 | neutral | None | None | None | None | N |
| R/K | 0.109 | likely_benign | 0.1354 | benign | -0.853 | Destabilizing | 0.148 | N | 0.215 | neutral | None | None | None | None | N |
| R/L | 0.1829 | likely_benign | 0.2364 | benign | 0.054 | Stabilizing | 0.001 | N | 0.187 | neutral | N | 0.419408751 | None | None | N |
| R/M | 0.2235 | likely_benign | 0.2996 | benign | -0.385 | Destabilizing | 0.596 | D | 0.424 | neutral | None | None | None | None | N |
| R/N | 0.3867 | ambiguous | 0.5034 | ambiguous | -0.397 | Destabilizing | 0.001 | N | 0.108 | neutral | None | None | None | None | N |
| R/P | 0.6067 | likely_pathogenic | 0.7259 | pathogenic | -0.244 | Destabilizing | 0.62 | D | 0.495 | neutral | N | 0.510702759 | None | None | N |
| R/Q | 0.1125 | likely_benign | 0.1477 | benign | -0.472 | Destabilizing | 0.296 | N | 0.264 | neutral | None | None | None | None | N |
| R/S | 0.3487 | ambiguous | 0.4677 | ambiguous | -1.215 | Destabilizing | 0.143 | N | 0.358 | neutral | N | 0.426814726 | None | None | N |
| R/T | 0.1869 | likely_benign | 0.2675 | benign | -0.857 | Destabilizing | 0.002 | N | 0.153 | neutral | None | None | None | None | N |
| R/V | 0.2296 | likely_benign | 0.289 | benign | -0.244 | Destabilizing | 0.001 | N | 0.239 | neutral | None | None | None | None | N |
| R/W | 0.1677 | likely_benign | 0.2257 | benign | -0.105 | Destabilizing | 0.972 | D | 0.459 | neutral | None | None | None | None | N |
| R/Y | 0.2896 | likely_benign | 0.3622 | ambiguous | 0.15 | Stabilizing | 0.296 | N | 0.489 | 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.