Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31082 | 93469;93470;93471 | chr2:178548382;178548381;178548380 | chr2:179413109;179413108;179413107 |
| N2AB | 29441 | 88546;88547;88548 | chr2:178548382;178548381;178548380 | chr2:179413109;179413108;179413107 |
| N2A | 28514 | 85765;85766;85767 | chr2:178548382;178548381;178548380 | chr2:179413109;179413108;179413107 |
| N2B | 22017 | 66274;66275;66276 | chr2:178548382;178548381;178548380 | chr2:179413109;179413108;179413107 |
| Novex-1 | 22142 | 66649;66650;66651 | chr2:178548382;178548381;178548380 | chr2:179413109;179413108;179413107 |
| Novex-2 | 22209 | 66850;66851;66852 | chr2:178548382;178548381;178548380 | chr2:179413109;179413108;179413107 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/D | None | None | 0.959 | N | 0.447 | 0.329 | 0.500488203797 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/K | rs199663613  |
0.405 | 0.992 | N | 0.448 | 0.344 | None | gnomAD-2.1.1 | 6.44E-05 | None | None | None | None | N | None | 5.78991E-04 | 2.83E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.57E-05 | 0 |
| E/K | rs199663613 |
0.405 | 0.992 | N | 0.448 | 0.344 | None | gnomAD-3.1.2 | 1.64296E-04 | None | None | None | None | N | None | 5.78983E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/K | rs199663613 |
0.405 | 0.992 | N | 0.448 | 0.344 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| E/K | rs199663613 |
0.405 | 0.992 | N | 0.448 | 0.344 | None | gnomAD-4.0.0 | 4.21347E-05 | None | None | None | None | N | None | 6.6624E-04 | 1.66633E-05 | None | 0 | 0 | None | 0 | 0 | 8.47585E-06 | 3.29388E-05 | 6.40143E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.1678 | likely_benign | 0.1535 | benign | -0.131 | Destabilizing | 0.826 | D | 0.371 | neutral | N | 0.466138091 | None | None | N |
| E/C | 0.8932 | likely_pathogenic | 0.8756 | pathogenic | 0.044 | Stabilizing | 0.999 | D | 0.479 | neutral | None | None | None | None | N |
| E/D | 0.3069 | likely_benign | 0.2978 | benign | -0.279 | Destabilizing | 0.959 | D | 0.447 | neutral | N | 0.510668394 | None | None | N |
| E/F | 0.8811 | likely_pathogenic | 0.8555 | pathogenic | -0.145 | Destabilizing | 0.991 | D | 0.495 | neutral | None | None | None | None | N |
| E/G | 0.3045 | likely_benign | 0.2819 | benign | -0.282 | Destabilizing | 0.959 | D | 0.483 | neutral | N | 0.510921884 | None | None | N |
| E/H | 0.7156 | likely_pathogenic | 0.6718 | pathogenic | 0.233 | Stabilizing | 0.1 | N | 0.248 | neutral | None | None | None | None | N |
| E/I | 0.4261 | ambiguous | 0.3878 | ambiguous | 0.215 | Stabilizing | 0.17 | N | 0.28 | neutral | None | None | None | None | N |
| E/K | 0.2913 | likely_benign | 0.233 | benign | 0.527 | Stabilizing | 0.992 | D | 0.448 | neutral | N | 0.49945022 | None | None | N |
| E/L | 0.5533 | ambiguous | 0.5097 | ambiguous | 0.215 | Stabilizing | 0.759 | D | 0.402 | neutral | None | None | None | None | N |
| E/M | 0.5852 | likely_pathogenic | 0.5352 | ambiguous | 0.175 | Stabilizing | 0.991 | D | 0.453 | neutral | None | None | None | None | N |
| E/N | 0.5036 | ambiguous | 0.4753 | ambiguous | 0.27 | Stabilizing | 0.939 | D | 0.429 | neutral | None | None | None | None | N |
| E/P | 0.4643 | ambiguous | 0.4254 | ambiguous | 0.119 | Stabilizing | 0.997 | D | 0.438 | neutral | None | None | None | None | N |
| E/Q | 0.2055 | likely_benign | 0.1841 | benign | 0.279 | Stabilizing | 0.983 | D | 0.486 | neutral | N | 0.483903632 | None | None | N |
| E/R | 0.4573 | ambiguous | 0.3773 | ambiguous | 0.689 | Stabilizing | 0.991 | D | 0.414 | neutral | None | None | None | None | N |
| E/S | 0.283 | likely_benign | 0.2607 | benign | 0.132 | Stabilizing | 0.969 | D | 0.405 | neutral | None | None | None | None | N |
| E/T | 0.3331 | likely_benign | 0.3131 | benign | 0.257 | Stabilizing | 0.969 | D | 0.46 | neutral | None | None | None | None | N |
| E/V | 0.244 | likely_benign | 0.2318 | benign | 0.119 | Stabilizing | 0.704 | D | 0.351 | neutral | N | 0.500464178 | None | None | N |
| E/W | 0.9689 | likely_pathogenic | 0.9601 | pathogenic | -0.063 | Destabilizing | 0.999 | D | 0.546 | neutral | None | None | None | None | N |
| E/Y | 0.8468 | likely_pathogenic | 0.8098 | pathogenic | 0.094 | Stabilizing | 0.982 | D | 0.487 | 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.