Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24035 | 72328;72329;72330 | chr2:178574029;178574028;178574027 | chr2:179438756;179438755;179438754 |
| N2AB | 22394 | 67405;67406;67407 | chr2:178574029;178574028;178574027 | chr2:179438756;179438755;179438754 |
| N2A | 21467 | 64624;64625;64626 | chr2:178574029;178574028;178574027 | chr2:179438756;179438755;179438754 |
| N2B | 14970 | 45133;45134;45135 | chr2:178574029;178574028;178574027 | chr2:179438756;179438755;179438754 |
| Novex-1 | 15095 | 45508;45509;45510 | chr2:178574029;178574028;178574027 | chr2:179438756;179438755;179438754 |
| Novex-2 | 15162 | 45709;45710;45711 | chr2:178574029;178574028;178574027 | chr2:179438756;179438755;179438754 |
| 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 | rs759861907  |
None | 0.988 | N | 0.509 | 0.395 | 0.542587012665 | gnomAD-4.0.0 | 5.47483E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.19672E-06 | 0 | 0 |
| F/Y | rs759861907 |
-0.611 | None | N | 0.151 | 0.086 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| F/Y | rs759861907 |
-0.611 | None | N | 0.151 | 0.086 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| F/Y | rs759861907 |
-0.611 | None | N | 0.151 | 0.086 | None | gnomAD-4.0.0 | 3.71905E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.0864E-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 | 0.8809 | likely_pathogenic | 0.8822 | pathogenic | -2.4 | Highly Destabilizing | 0.575 | D | 0.423 | neutral | None | None | None | None | I |
| F/C | 0.6006 | likely_pathogenic | 0.6281 | pathogenic | -1.568 | Destabilizing | 0.988 | D | 0.509 | neutral | N | 0.499069643 | None | None | I |
| F/D | 0.8938 | likely_pathogenic | 0.8996 | pathogenic | -2.524 | Highly Destabilizing | 0.906 | D | 0.549 | neutral | None | None | None | None | I |
| F/E | 0.9395 | likely_pathogenic | 0.9389 | pathogenic | -2.333 | Highly Destabilizing | 0.906 | D | 0.531 | neutral | None | None | None | None | I |
| F/G | 0.8893 | likely_pathogenic | 0.8883 | pathogenic | -2.838 | Highly Destabilizing | 0.906 | D | 0.487 | neutral | None | None | None | None | I |
| F/H | 0.688 | likely_pathogenic | 0.7008 | pathogenic | -1.41 | Destabilizing | 0.826 | D | 0.443 | neutral | None | None | None | None | I |
| F/I | 0.6168 | likely_pathogenic | 0.6061 | pathogenic | -1.002 | Destabilizing | 0.505 | D | 0.439 | neutral | N | 0.484374589 | None | None | I |
| F/K | 0.943 | likely_pathogenic | 0.9423 | pathogenic | -1.741 | Destabilizing | 0.826 | D | 0.534 | neutral | None | None | None | None | I |
| F/L | 0.9159 | likely_pathogenic | 0.9268 | pathogenic | -1.002 | Destabilizing | 0.174 | N | 0.458 | neutral | N | 0.429499954 | None | None | I |
| F/M | 0.7414 | likely_pathogenic | 0.7391 | pathogenic | -0.784 | Destabilizing | 0.967 | D | 0.457 | neutral | None | None | None | None | I |
| F/N | 0.7484 | likely_pathogenic | 0.7692 | pathogenic | -2.143 | Highly Destabilizing | 0.906 | D | 0.548 | neutral | None | None | None | None | I |
| F/P | 0.9928 | likely_pathogenic | 0.9925 | pathogenic | -1.474 | Destabilizing | 0.967 | D | 0.546 | neutral | None | None | None | None | I |
| F/Q | 0.8925 | likely_pathogenic | 0.8938 | pathogenic | -2.082 | Highly Destabilizing | 0.906 | D | 0.546 | neutral | None | None | None | None | I |
| F/R | 0.9026 | likely_pathogenic | 0.9073 | pathogenic | -1.333 | Destabilizing | 0.906 | D | 0.548 | neutral | None | None | None | None | I |
| F/S | 0.7643 | likely_pathogenic | 0.78 | pathogenic | -2.821 | Highly Destabilizing | 0.782 | D | 0.454 | neutral | N | 0.486699379 | None | None | I |
| F/T | 0.8801 | likely_pathogenic | 0.8704 | pathogenic | -2.514 | Highly Destabilizing | 0.906 | D | 0.456 | neutral | None | None | None | None | I |
| F/V | 0.6161 | likely_pathogenic | 0.6123 | pathogenic | -1.474 | Destabilizing | 0.505 | D | 0.385 | neutral | D | 0.523682339 | None | None | I |
| F/W | 0.4782 | ambiguous | 0.4859 | ambiguous | -0.185 | Destabilizing | 0.906 | D | 0.49 | neutral | None | None | None | None | I |
| F/Y | 0.0805 | likely_benign | 0.0913 | benign | -0.491 | Destabilizing | None | N | 0.151 | neutral | N | 0.485934814 | None | None | I |
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.