Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9980 | 30163;30164;30165 | chr2:178704534;178704533;178704532 | chr2:179569261;179569260;179569259 |
| N2AB | 9663 | 29212;29213;29214 | chr2:178704534;178704533;178704532 | chr2:179569261;179569260;179569259 |
| N2A | 8736 | 26431;26432;26433 | chr2:178704534;178704533;178704532 | chr2:179569261;179569260;179569259 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | rs189286381  |
-0.935 | 0.18 | None | 0.315 | 0.185 | None | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.00067E-04 | None | 0 | 1.56E-05 | 0 |
| A/S | rs189286381 |
-0.935 | 0.18 | None | 0.315 | 0.185 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/S | rs189286381 |
-0.935 | 0.18 | None | 0.315 | 0.185 | None | gnomAD-4.0.0 | 1.61366E-05 | None | None | None | None | N | None | 1.33733E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69706E-05 | 5.52303E-05 | 0 |
| A/T | rs189286381 |
-0.875 | 0.977 | None | 0.571 | 0.177 | None | gnomAD-2.1.1 | 6.02544E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 8.05624E-03 | None | 3.002E-04 | None | 0 | 7.82E-06 | 1.41283E-04 |
| A/T | rs189286381 |
-0.875 | 0.977 | None | 0.571 | 0.177 | None | gnomAD-3.1.2 | 3.15449E-04 | None | None | None | None | N | None | 0 | 6.55E-05 | 1.42544E-02 | 0 | 5.95925E-03 | None | 0 | 0 | 1.47E-05 | 4.13736E-04 | 0 |
| A/T | rs189286381 |
-0.875 | 0.977 | None | 0.571 | 0.177 | None | 1000 genomes | 9.98403E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 5E-03 | 0 | None | None | None | 0 | None |
| A/T | rs189286381 |
-0.875 | 0.977 | None | 0.571 | 0.177 | None |
Sasaki (2020)
| None |
Other 
|
comp het with A19938T, R29293C | None | None | N | Genetic analysis of 2 siblings with asymmetric facial and limb weakness; variant prioritisation; no validation | None | None | None | None | None | None | None | None | None | None | None |
| A/T | rs189286381 |
-0.875 | 0.977 | None | 0.571 | 0.177 | None | gnomAD-4.0.0 | 1.97969E-04 | None | None | None | None | N | None | 0 | 1.67325E-05 | None | 0 | 5.83987E-03 | None | 0 | 1.65344E-04 | 1.18795E-05 | 2.20931E-04 | 1.28242E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.873 | likely_pathogenic | 0.8919 | pathogenic | -0.857 | Destabilizing | 0.999 | D | 0.731 | prob.delet. | None | None | None | None | N |
| A/D | 0.9898 | likely_pathogenic | 0.9708 | pathogenic | -1.436 | Destabilizing | 0.982 | D | 0.743 | deleterious | None | None | None | None | N |
| A/E | 0.9771 | likely_pathogenic | 0.9482 | pathogenic | -1.374 | Destabilizing | 0.953 | D | 0.675 | neutral | None | None | None | None | N |
| A/F | 0.9357 | likely_pathogenic | 0.919 | pathogenic | -0.825 | Destabilizing | 0.998 | D | 0.784 | deleterious | None | None | None | None | N |
| A/G | 0.6297 | likely_pathogenic | 0.5774 | pathogenic | -1.276 | Destabilizing | 0.76 | D | 0.578 | neutral | None | None | None | None | N |
| A/H | 0.9761 | likely_pathogenic | 0.9611 | pathogenic | -1.549 | Destabilizing | 0.999 | D | 0.777 | deleterious | None | None | None | None | N |
| A/I | 0.9264 | likely_pathogenic | 0.8876 | pathogenic | -0.052 | Destabilizing | 0.993 | D | 0.753 | deleterious | None | None | None | None | N |
| A/K | 0.9898 | likely_pathogenic | 0.9776 | pathogenic | -1.28 | Destabilizing | 0.953 | D | 0.671 | neutral | None | None | None | None | N |
| A/L | 0.8548 | likely_pathogenic | 0.8076 | pathogenic | -0.052 | Destabilizing | 0.953 | D | 0.651 | neutral | None | None | None | None | N |
| A/M | 0.8995 | likely_pathogenic | 0.8632 | pathogenic | -0.074 | Destabilizing | 0.999 | D | 0.757 | deleterious | None | None | None | None | N |
| A/N | 0.9627 | likely_pathogenic | 0.9365 | pathogenic | -1.165 | Destabilizing | 0.986 | D | 0.741 | deleterious | None | None | None | None | N |
| A/P | 0.998 | likely_pathogenic | 0.995 | pathogenic | -0.296 | Destabilizing | 0.996 | D | 0.745 | deleterious | None | None | None | None | N |
| A/Q | 0.9457 | likely_pathogenic | 0.9162 | pathogenic | -1.173 | Destabilizing | 0.993 | D | 0.767 | deleterious | None | None | None | None | N |
| A/R | 0.9705 | likely_pathogenic | 0.9411 | pathogenic | -1.089 | Destabilizing | 0.986 | D | 0.759 | deleterious | None | None | None | None | N |
| A/S | 0.2437 | likely_benign | 0.2029 | benign | -1.552 | Destabilizing | 0.18 | N | 0.315 | neutral | None | None | None | None | N |
| A/T | 0.5308 | ambiguous | 0.417 | ambiguous | -1.373 | Destabilizing | 0.977 | D | 0.571 | neutral | None | None | None | None | N |
| A/V | 0.747 | likely_pathogenic | 0.664 | pathogenic | -0.296 | Destabilizing | 0.939 | D | 0.625 | neutral | None | None | None | None | N |
| A/W | 0.9951 | likely_pathogenic | 0.9922 | pathogenic | -1.351 | Destabilizing | 0.999 | D | 0.78 | deleterious | None | None | None | None | N |
| A/Y | 0.975 | likely_pathogenic | 0.9647 | pathogenic | -0.852 | Destabilizing | 0.998 | D | 0.786 | deleterious | 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.