Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17629 | 53110;53111;53112 | chr2:178607902;178607901;178607900 | chr2:179472629;179472628;179472627 |
| N2AB | 15988 | 48187;48188;48189 | chr2:178607902;178607901;178607900 | chr2:179472629;179472628;179472627 |
| N2A | 15061 | 45406;45407;45408 | chr2:178607902;178607901;178607900 | chr2:179472629;179472628;179472627 |
| N2B | 8564 | 25915;25916;25917 | chr2:178607902;178607901;178607900 | chr2:179472629;179472628;179472627 |
| Novex-1 | 8689 | 26290;26291;26292 | chr2:178607902;178607901;178607900 | chr2:179472629;179472628;179472627 |
| Novex-2 | 8756 | 26491;26492;26493 | chr2:178607902;178607901;178607900 | chr2:179472629;179472628;179472627 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs1039650213  |
None | 0.915 | N | 0.601 | 0.353 | 0.499793596984 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/C | rs1039650213 |
None | 0.915 | N | 0.601 | 0.353 | 0.499793596984 | gnomAD-4.0.0 | 3.04544E-06 | None | None | None | None | N | None | 0 | 6.16827E-05 | None | 0 | 0 | None | 0 | 0 | 1.20507E-06 | 0 | 3.40252E-05 |
| Y/F | None | None | None | N | 0.168 | 0.074 | 0.220303561663 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.8928 | likely_pathogenic | 0.8544 | pathogenic | -2.176 | Highly Destabilizing | 0.149 | N | 0.492 | neutral | None | None | None | None | N |
| Y/C | 0.3325 | likely_benign | 0.2483 | benign | -1.366 | Destabilizing | 0.915 | D | 0.601 | neutral | N | 0.500437333 | None | None | N |
| Y/D | 0.9199 | likely_pathogenic | 0.9014 | pathogenic | -1.522 | Destabilizing | 0.741 | D | 0.615 | neutral | N | 0.5151423 | None | None | N |
| Y/E | 0.9619 | likely_pathogenic | 0.9462 | pathogenic | -1.376 | Destabilizing | 0.555 | D | 0.573 | neutral | None | None | None | None | N |
| Y/F | 0.0859 | likely_benign | 0.0854 | benign | -0.749 | Destabilizing | None | N | 0.168 | neutral | N | 0.437463289 | None | None | N |
| Y/G | 0.8657 | likely_pathogenic | 0.829 | pathogenic | -2.531 | Highly Destabilizing | 0.555 | D | 0.591 | neutral | None | None | None | None | N |
| Y/H | 0.4847 | ambiguous | 0.4135 | ambiguous | -1.037 | Destabilizing | 0.741 | D | 0.491 | neutral | D | 0.52441027 | None | None | N |
| Y/I | 0.7439 | likely_pathogenic | 0.6751 | pathogenic | -1.066 | Destabilizing | 0.081 | N | 0.444 | neutral | None | None | None | None | N |
| Y/K | 0.9206 | likely_pathogenic | 0.8916 | pathogenic | -1.647 | Destabilizing | 0.555 | D | 0.573 | neutral | None | None | None | None | N |
| Y/L | 0.6729 | likely_pathogenic | 0.6001 | pathogenic | -1.066 | Destabilizing | 0.035 | N | 0.444 | neutral | None | None | None | None | N |
| Y/M | 0.7887 | likely_pathogenic | 0.734 | pathogenic | -0.945 | Destabilizing | 0.555 | D | 0.545 | neutral | None | None | None | None | N |
| Y/N | 0.7379 | likely_pathogenic | 0.7058 | pathogenic | -2.266 | Highly Destabilizing | 0.741 | D | 0.595 | neutral | N | 0.514888811 | None | None | N |
| Y/P | 0.9954 | likely_pathogenic | 0.9938 | pathogenic | -1.437 | Destabilizing | 0.791 | D | 0.633 | neutral | None | None | None | None | N |
| Y/Q | 0.9031 | likely_pathogenic | 0.865 | pathogenic | -2.026 | Highly Destabilizing | 0.791 | D | 0.539 | neutral | None | None | None | None | N |
| Y/R | 0.8692 | likely_pathogenic | 0.8272 | pathogenic | -1.436 | Destabilizing | 0.555 | D | 0.599 | neutral | None | None | None | None | N |
| Y/S | 0.8159 | likely_pathogenic | 0.7764 | pathogenic | -2.704 | Highly Destabilizing | 0.484 | N | 0.559 | neutral | N | 0.49669565 | None | None | N |
| Y/T | 0.8989 | likely_pathogenic | 0.8724 | pathogenic | -2.445 | Highly Destabilizing | 0.555 | D | 0.564 | neutral | None | None | None | None | N |
| Y/V | 0.6709 | likely_pathogenic | 0.6064 | pathogenic | -1.437 | Destabilizing | 0.081 | N | 0.428 | neutral | None | None | None | None | N |
| Y/W | 0.594 | likely_pathogenic | 0.5232 | ambiguous | -0.291 | Destabilizing | 0.555 | 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.