Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18550 | 55873;55874;55875 | chr2:178601349;178601348;178601347 | chr2:179466076;179466075;179466074 |
| N2AB | 16909 | 50950;50951;50952 | chr2:178601349;178601348;178601347 | chr2:179466076;179466075;179466074 |
| N2A | 15982 | 48169;48170;48171 | chr2:178601349;178601348;178601347 | chr2:179466076;179466075;179466074 |
| N2B | 9485 | 28678;28679;28680 | chr2:178601349;178601348;178601347 | chr2:179466076;179466075;179466074 |
| Novex-1 | 9610 | 29053;29054;29055 | chr2:178601349;178601348;178601347 | chr2:179466076;179466075;179466074 |
| Novex-2 | 9677 | 29254;29255;29256 | chr2:178601349;178601348;178601347 | chr2:179466076;179466075;179466074 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/C | rs553264256  |
-0.99 | 1.0 | N | 0.734 | 0.485 | 0.781294814779 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07469E-04 | 0 |
| F/C | rs553264256 |
-0.99 | 1.0 | N | 0.734 | 0.485 | 0.781294814779 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| F/C | rs553264256 |
-0.99 | 1.0 | N | 0.734 | 0.485 | 0.781294814779 | gnomAD-4.0.0 | 6.57358E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07641E-04 | 0 |
| F/L | rs1248662230 |
-1.761 | 0.061 | N | 0.337 | 0.236 | 0.384584525793 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| F/L | rs1248662230 |
-1.761 | 0.061 | N | 0.337 | 0.236 | 0.384584525793 | gnomAD-4.0.0 | 1.5964E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86717E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.7625 | likely_pathogenic | 0.7212 | pathogenic | -2.29 | Highly Destabilizing | 0.993 | D | 0.651 | neutral | None | None | None | None | N |
| F/C | 0.4223 | ambiguous | 0.3695 | ambiguous | -1.002 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | N | 0.493295143 | None | None | N |
| F/D | 0.9344 | likely_pathogenic | 0.927 | pathogenic | -2.149 | Highly Destabilizing | 0.999 | D | 0.773 | deleterious | None | None | None | None | N |
| F/E | 0.9225 | likely_pathogenic | 0.9204 | pathogenic | -1.941 | Destabilizing | 0.999 | D | 0.757 | deleterious | None | None | None | None | N |
| F/G | 0.92 | likely_pathogenic | 0.9119 | pathogenic | -2.716 | Highly Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | N |
| F/H | 0.5975 | likely_pathogenic | 0.5947 | pathogenic | -1.288 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| F/I | 0.3513 | ambiguous | 0.26 | benign | -0.918 | Destabilizing | 0.961 | D | 0.609 | neutral | N | 0.437113786 | None | None | N |
| F/K | 0.9311 | likely_pathogenic | 0.9257 | pathogenic | -1.282 | Destabilizing | 0.999 | D | 0.738 | prob.delet. | None | None | None | None | N |
| F/L | 0.819 | likely_pathogenic | 0.7419 | pathogenic | -0.918 | Destabilizing | 0.061 | N | 0.337 | neutral | N | 0.391418782 | None | None | N |
| F/M | 0.6164 | likely_pathogenic | 0.5645 | pathogenic | -0.633 | Destabilizing | 0.996 | D | 0.638 | neutral | None | None | None | None | N |
| F/N | 0.7962 | likely_pathogenic | 0.7985 | pathogenic | -1.683 | Destabilizing | 0.999 | D | 0.784 | deleterious | None | None | None | None | N |
| F/P | 0.9988 | likely_pathogenic | 0.9986 | pathogenic | -1.383 | Destabilizing | 0.999 | D | 0.781 | deleterious | None | None | None | None | N |
| F/Q | 0.8321 | likely_pathogenic | 0.8301 | pathogenic | -1.598 | Destabilizing | 0.999 | D | 0.783 | deleterious | None | None | None | None | N |
| F/R | 0.8423 | likely_pathogenic | 0.8273 | pathogenic | -0.991 | Destabilizing | 0.999 | D | 0.78 | deleterious | None | None | None | None | N |
| F/S | 0.6473 | likely_pathogenic | 0.6061 | pathogenic | -2.347 | Highly Destabilizing | 0.999 | D | 0.651 | neutral | N | 0.445442481 | None | None | N |
| F/T | 0.7002 | likely_pathogenic | 0.6766 | pathogenic | -2.034 | Highly Destabilizing | 0.998 | D | 0.661 | neutral | None | None | None | None | N |
| F/V | 0.3394 | likely_benign | 0.2599 | benign | -1.383 | Destabilizing | 0.961 | D | 0.629 | neutral | N | 0.413543493 | None | None | N |
| F/W | 0.6043 | likely_pathogenic | 0.5589 | ambiguous | 0.078 | Stabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| F/Y | 0.1308 | likely_benign | 0.1269 | benign | -0.262 | Destabilizing | 0.997 | D | 0.599 | neutral | N | 0.421490972 | 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.