Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34308 | 103147;103148;103149 | chr2:178533693;178533692;178533691 | chr2:179398420;179398419;179398418 |
| N2AB | 32667 | 98224;98225;98226 | chr2:178533693;178533692;178533691 | chr2:179398420;179398419;179398418 |
| N2A | 31740 | 95443;95444;95445 | chr2:178533693;178533692;178533691 | chr2:179398420;179398419;179398418 |
| N2B | 25243 | 75952;75953;75954 | chr2:178533693;178533692;178533691 | chr2:179398420;179398419;179398418 |
| Novex-1 | 25368 | 76327;76328;76329 | chr2:178533693;178533692;178533691 | chr2:179398420;179398419;179398418 |
| Novex-2 | 25435 | 76528;76529;76530 | chr2:178533693;178533692;178533691 | chr2:179398420;179398419;179398418 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs528711725  |
0.115 | 0.001 | N | 0.262 | 0.146 | 0.117506650769 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.6715E-04 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs528711725 |
0.115 | 0.001 | N | 0.262 | 0.146 | 0.117506650769 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92382E-04 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs528711725 |
0.115 | 0.001 | N | 0.262 | 0.146 | 0.117506650769 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| T/I | rs528711725 |
0.115 | 0.001 | N | 0.262 | 0.146 | 0.117506650769 | gnomAD-4.0.0 | 3.84214E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 7.27273E-05 | None | 0 | 0 | 0 | 0 | 0 |
| T/P | rs769739303 |
-0.532 | 0.484 | N | 0.44 | 0.189 | 0.337621943819 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.22866E-04 | None | 0 | None | 0 | 0 | 0 |
| T/P | rs769739303 |
-0.532 | 0.484 | N | 0.44 | 0.189 | 0.337621943819 | gnomAD-4.0.0 | 1.90927E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.32742E-04 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0797 | likely_benign | 0.086 | benign | -1.039 | Destabilizing | None | N | 0.197 | neutral | N | 0.492903646 | None | None | N |
| T/C | 0.2993 | likely_benign | 0.3365 | benign | -0.72 | Destabilizing | 0.824 | D | 0.437 | neutral | None | None | None | None | N |
| T/D | 0.3143 | likely_benign | 0.3484 | ambiguous | -0.673 | Destabilizing | 0.38 | N | 0.406 | neutral | None | None | None | None | N |
| T/E | 0.2614 | likely_benign | 0.276 | benign | -0.617 | Destabilizing | 0.081 | N | 0.407 | neutral | None | None | None | None | N |
| T/F | 0.1761 | likely_benign | 0.2052 | benign | -1.081 | Destabilizing | 0.38 | N | 0.521 | neutral | None | None | None | None | N |
| T/G | 0.2435 | likely_benign | 0.285 | benign | -1.345 | Destabilizing | 0.081 | N | 0.441 | neutral | None | None | None | None | N |
| T/H | 0.1576 | likely_benign | 0.164 | benign | -1.677 | Destabilizing | 0.824 | D | 0.51 | neutral | None | None | None | None | N |
| T/I | 0.0777 | likely_benign | 0.0915 | benign | -0.293 | Destabilizing | 0.001 | N | 0.262 | neutral | N | 0.475896753 | None | None | N |
| T/K | 0.1575 | likely_benign | 0.1693 | benign | -0.751 | Destabilizing | 0.062 | N | 0.41 | neutral | N | 0.424734426 | None | None | N |
| T/L | 0.0731 | likely_benign | 0.0862 | benign | -0.293 | Destabilizing | 0.012 | N | 0.379 | neutral | None | None | None | None | N |
| T/M | 0.089 | likely_benign | 0.0979 | benign | 0.052 | Stabilizing | 0.38 | N | 0.452 | neutral | None | None | None | None | N |
| T/N | 0.1111 | likely_benign | 0.1264 | benign | -0.924 | Destabilizing | 0.235 | N | 0.387 | neutral | None | None | None | None | N |
| T/P | 0.5602 | ambiguous | 0.5919 | pathogenic | -0.509 | Destabilizing | 0.484 | N | 0.44 | neutral | N | 0.509343673 | None | None | N |
| T/Q | 0.1804 | likely_benign | 0.1886 | benign | -1.021 | Destabilizing | 0.38 | N | 0.457 | neutral | None | None | None | None | N |
| T/R | 0.1122 | likely_benign | 0.1228 | benign | -0.644 | Destabilizing | 0.317 | N | 0.449 | neutral | N | 0.439242519 | None | None | N |
| T/S | 0.0957 | likely_benign | 0.1049 | benign | -1.202 | Destabilizing | None | N | 0.26 | neutral | N | 0.462676739 | None | None | N |
| T/V | 0.0862 | likely_benign | 0.0979 | benign | -0.509 | Destabilizing | 0.001 | N | 0.273 | neutral | None | None | None | None | N |
| T/W | 0.5049 | ambiguous | 0.5565 | ambiguous | -1.035 | Destabilizing | 0.935 | D | 0.606 | neutral | None | None | None | None | N |
| T/Y | 0.2303 | likely_benign | 0.2515 | benign | -0.764 | Destabilizing | 0.555 | D | 0.521 | 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.