Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3393 | 10402;10403;10404 | chr2:178759110;178759109;178759108 | chr2:179623837;179623836;179623835 |
| N2AB | 3393 | 10402;10403;10404 | chr2:178759110;178759109;178759108 | chr2:179623837;179623836;179623835 |
| N2A | 3393 | 10402;10403;10404 | chr2:178759110;178759109;178759108 | chr2:179623837;179623836;179623835 |
| N2B | 3347 | 10264;10265;10266 | chr2:178759110;178759109;178759108 | chr2:179623837;179623836;179623835 |
| Novex-1 | 3347 | 10264;10265;10266 | chr2:178759110;178759109;178759108 | chr2:179623837;179623836;179623835 |
| Novex-2 | 3347 | 10264;10265;10266 | chr2:178759110;178759109;178759108 | chr2:179623837;179623836;179623835 |
| Novex-3 | 3393 | 10402;10403;10404 | chr2:178759110;178759109;178759108 | chr2:179623837;179623836;179623835 |
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 | rs752227022  |
0.18 | 0.994 | N | 0.465 | 0.57 | 0.61879682266 | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.77E-05 | 0 |
| T/I | rs752227022 |
0.18 | 0.994 | N | 0.465 | 0.57 | 0.61879682266 | gnomAD-4.0.0 | 2.73646E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79867E-06 | 1.15937E-05 | 1.65596E-05 |
| T/S | rs752227022 |
-1.197 | 0.287 | N | 0.193 | 0.29 | 0.202949470691 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 0 | 0 |
| T/S | rs752227022 |
-1.197 | 0.287 | N | 0.193 | 0.29 | 0.202949470691 | gnomAD-4.0.0 | 6.84114E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52105E-05 | 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 | 0.1265 | likely_benign | 0.1586 | benign | -0.445 | Destabilizing | 0.835 | D | 0.363 | neutral | N | 0.513354809 | None | None | N |
| T/C | 0.7324 | likely_pathogenic | 0.7394 | pathogenic | -0.282 | Destabilizing | 1.0 | D | 0.509 | neutral | None | None | None | None | N |
| T/D | 0.5183 | ambiguous | 0.5897 | pathogenic | -0.078 | Destabilizing | 0.97 | D | 0.448 | neutral | None | None | None | None | N |
| T/E | 0.3556 | ambiguous | 0.4664 | ambiguous | -0.121 | Destabilizing | 0.97 | D | 0.453 | neutral | None | None | None | None | N |
| T/F | 0.3575 | ambiguous | 0.3985 | ambiguous | -0.666 | Destabilizing | 0.999 | D | 0.587 | neutral | None | None | None | None | N |
| T/G | 0.3899 | ambiguous | 0.444 | ambiguous | -0.647 | Destabilizing | 0.97 | D | 0.465 | neutral | None | None | None | None | N |
| T/H | 0.3081 | likely_benign | 0.3544 | ambiguous | -0.937 | Destabilizing | 1.0 | D | 0.571 | neutral | None | None | None | None | N |
| T/I | 0.2516 | likely_benign | 0.3263 | benign | -0.018 | Destabilizing | 0.994 | D | 0.465 | neutral | N | 0.512807079 | None | None | N |
| T/K | 0.2618 | likely_benign | 0.332 | benign | -0.62 | Destabilizing | 0.97 | D | 0.446 | neutral | None | None | None | None | N |
| T/L | 0.1542 | likely_benign | 0.1705 | benign | -0.018 | Destabilizing | 0.985 | D | 0.43 | neutral | None | None | None | None | N |
| T/M | 0.1241 | likely_benign | 0.1237 | benign | 0.119 | Stabilizing | 1.0 | D | 0.505 | neutral | None | None | None | None | N |
| T/N | 0.1698 | likely_benign | 0.186 | benign | -0.394 | Destabilizing | 0.961 | D | 0.457 | neutral | N | 0.513961416 | None | None | N |
| T/P | 0.561 | ambiguous | 0.6617 | pathogenic | -0.129 | Destabilizing | 0.994 | D | 0.467 | neutral | D | 0.600268502 | None | None | N |
| T/Q | 0.2578 | likely_benign | 0.3175 | benign | -0.583 | Destabilizing | 0.996 | D | 0.499 | neutral | None | None | None | None | N |
| T/R | 0.2158 | likely_benign | 0.2615 | benign | -0.34 | Destabilizing | 0.996 | D | 0.486 | neutral | None | None | None | None | N |
| T/S | 0.1409 | likely_benign | 0.1467 | benign | -0.593 | Destabilizing | 0.287 | N | 0.193 | neutral | N | 0.440486096 | None | None | N |
| T/V | 0.2246 | likely_benign | 0.2838 | benign | -0.129 | Destabilizing | 0.985 | D | 0.437 | neutral | None | None | None | None | N |
| T/W | 0.7411 | likely_pathogenic | 0.7506 | pathogenic | -0.666 | Destabilizing | 1.0 | D | 0.607 | neutral | None | None | None | None | N |
| T/Y | 0.4121 | ambiguous | 0.4619 | ambiguous | -0.423 | Destabilizing | 0.999 | D | 0.593 | 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.