Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22761 | 68506;68507;68508 | chr2:178578659;178578658;178578657 | chr2:179443386;179443385;179443384 |
| N2AB | 21120 | 63583;63584;63585 | chr2:178578659;178578658;178578657 | chr2:179443386;179443385;179443384 |
| N2A | 20193 | 60802;60803;60804 | chr2:178578659;178578658;178578657 | chr2:179443386;179443385;179443384 |
| N2B | 13696 | 41311;41312;41313 | chr2:178578659;178578658;178578657 | chr2:179443386;179443385;179443384 |
| Novex-1 | 13821 | 41686;41687;41688 | chr2:178578659;178578658;178578657 | chr2:179443386;179443385;179443384 |
| Novex-2 | 13888 | 41887;41888;41889 | chr2:178578659;178578658;178578657 | chr2:179443386;179443385;179443384 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | rs2047006376  |
None | None | N | 0.186 | 0.056 | 0.0611884634855 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/A | rs2047006376 |
None | None | N | 0.186 | 0.056 | 0.0611884634855 | gnomAD-4.0.0 | 6.57566E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47085E-05 | 0 | 0 |
| S/F | rs397517676 |
None | 0.427 | N | 0.584 | 0.178 | 0.440394187108 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0903 | likely_benign | 0.0873 | benign | -0.717 | Destabilizing | None | N | 0.186 | neutral | N | 0.482752862 | None | None | N |
| S/C | 0.0942 | likely_benign | 0.0906 | benign | -0.718 | Destabilizing | 0.602 | D | 0.545 | neutral | N | 0.472916175 | None | None | N |
| S/D | 0.6154 | likely_pathogenic | 0.5881 | pathogenic | -0.927 | Destabilizing | 0.124 | N | 0.425 | neutral | None | None | None | None | N |
| S/E | 0.66 | likely_pathogenic | 0.6422 | pathogenic | -0.864 | Destabilizing | 0.22 | N | 0.407 | neutral | None | None | None | None | N |
| S/F | 0.1473 | likely_benign | 0.1382 | benign | -0.731 | Destabilizing | 0.427 | N | 0.584 | neutral | N | 0.511998334 | None | None | N |
| S/G | 0.1392 | likely_benign | 0.1262 | benign | -1.02 | Destabilizing | 0.055 | N | 0.368 | neutral | None | None | None | None | N |
| S/H | 0.3223 | likely_benign | 0.2964 | benign | -1.486 | Destabilizing | 0.667 | D | 0.547 | neutral | None | None | None | None | N |
| S/I | 0.1248 | likely_benign | 0.1139 | benign | -0.001 | Destabilizing | 0.002 | N | 0.398 | neutral | None | None | None | None | N |
| S/K | 0.7384 | likely_pathogenic | 0.6926 | pathogenic | -0.69 | Destabilizing | 0.22 | N | 0.407 | neutral | None | None | None | None | N |
| S/L | 0.0845 | likely_benign | 0.079 | benign | -0.001 | Destabilizing | 0.025 | N | 0.425 | neutral | None | None | None | None | N |
| S/M | 0.1573 | likely_benign | 0.133 | benign | 0.1 | Stabilizing | 0.025 | N | 0.366 | neutral | None | None | None | None | N |
| S/N | 0.1675 | likely_benign | 0.1441 | benign | -0.921 | Destabilizing | 0.001 | N | 0.324 | neutral | None | None | None | None | N |
| S/P | 0.8763 | likely_pathogenic | 0.8386 | pathogenic | -0.205 | Destabilizing | 0.301 | N | 0.579 | neutral | N | 0.477435625 | None | None | N |
| S/Q | 0.5289 | ambiguous | 0.4814 | ambiguous | -0.987 | Destabilizing | 0.667 | D | 0.519 | neutral | None | None | None | None | N |
| S/R | 0.6378 | likely_pathogenic | 0.6192 | pathogenic | -0.706 | Destabilizing | 0.22 | N | 0.542 | neutral | None | None | None | None | N |
| S/T | 0.0783 | likely_benign | 0.0699 | benign | -0.787 | Destabilizing | 0.001 | N | 0.206 | neutral | N | 0.374102457 | None | None | N |
| S/V | 0.1438 | likely_benign | 0.1275 | benign | -0.205 | Destabilizing | 0.055 | N | 0.444 | neutral | None | None | None | None | N |
| S/W | 0.2978 | likely_benign | 0.3078 | benign | -0.791 | Destabilizing | 0.958 | D | 0.635 | neutral | None | None | None | None | N |
| S/Y | 0.1462 | likely_benign | 0.1476 | benign | -0.461 | Destabilizing | 0.822 | D | 0.555 | neutral | N | 0.502032056 | 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.