Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31060 | 93403;93404;93405 | chr2:178548448;178548447;178548446 | chr2:179413175;179413174;179413173 |
| N2AB | 29419 | 88480;88481;88482 | chr2:178548448;178548447;178548446 | chr2:179413175;179413174;179413173 |
| N2A | 28492 | 85699;85700;85701 | chr2:178548448;178548447;178548446 | chr2:179413175;179413174;179413173 |
| N2B | 21995 | 66208;66209;66210 | chr2:178548448;178548447;178548446 | chr2:179413175;179413174;179413173 |
| Novex-1 | 22120 | 66583;66584;66585 | chr2:178548448;178548447;178548446 | chr2:179413175;179413174;179413173 |
| Novex-2 | 22187 | 66784;66785;66786 | chr2:178548448;178548447;178548446 | chr2:179413175;179413174;179413173 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs750303653  |
-0.476 | 1.0 | N | 0.723 | 0.506 | 0.753210536836 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 9.8E-05 | None | 0 | 8.92E-06 | 1.65782E-04 |
| R/C | rs750303653 |
-0.476 | 1.0 | N | 0.723 | 0.506 | 0.753210536836 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07297E-04 | 0 |
| R/C | rs750303653 |
-0.476 | 1.0 | N | 0.723 | 0.506 | 0.753210536836 | gnomAD-4.0.0 | 1.92106E-05 | None | None | None | None | N | None | 0 | 5.00083E-05 | None | 0 | 0 | None | 0 | 0 | 1.18663E-05 | 1.42741E-04 | 1.60102E-05 |
| R/H | rs776018262 |
-1.298 | 1.0 | N | 0.667 | 0.455 | 0.323342291347 | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | N | None | 4.13E-05 | 2.83E-05 | None | 0 | 5.13E-05 | None | 3.27E-05 | None | 0 | 1.57E-05 | 0 |
| R/H | rs776018262 |
-1.298 | 1.0 | N | 0.667 | 0.455 | 0.323342291347 | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 4.83E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/H | rs776018262 |
-1.298 | 1.0 | N | 0.667 | 0.455 | 0.323342291347 | gnomAD-4.0.0 | 2.54071E-05 | None | None | None | None | N | None | 4.00491E-05 | 3.33411E-05 | None | 0 | 0 | None | 0 | 0 | 2.28852E-05 | 7.68521E-05 | 3.20195E-05 |
| R/S | None | None | 1.0 | N | 0.585 | 0.452 | 0.400756358115 | gnomAD-4.0.0 | 6.84187E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99442E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9171 | likely_pathogenic | 0.8574 | pathogenic | -0.483 | Destabilizing | 0.999 | D | 0.443 | neutral | None | None | None | None | N |
| R/C | 0.4435 | ambiguous | 0.3779 | ambiguous | -0.506 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.514098208 | None | None | N |
| R/D | 0.9854 | likely_pathogenic | 0.9708 | pathogenic | -0.07 | Destabilizing | 1.0 | D | 0.62 | neutral | None | None | None | None | N |
| R/E | 0.9169 | likely_pathogenic | 0.8597 | pathogenic | -0.01 | Destabilizing | 0.999 | D | 0.488 | neutral | None | None | None | None | N |
| R/F | 0.9146 | likely_pathogenic | 0.8668 | pathogenic | -0.706 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/G | 0.7916 | likely_pathogenic | 0.6584 | pathogenic | -0.686 | Destabilizing | 1.0 | D | 0.527 | neutral | N | 0.519958882 | None | None | N |
| R/H | 0.276 | likely_benign | 0.2031 | benign | -1.032 | Destabilizing | 1.0 | D | 0.667 | neutral | N | 0.47834377 | None | None | N |
| R/I | 0.8565 | likely_pathogenic | 0.7898 | pathogenic | 0.025 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/K | 0.2891 | likely_benign | 0.219 | benign | -0.478 | Destabilizing | 0.998 | D | 0.384 | neutral | None | None | None | None | N |
| R/L | 0.6742 | likely_pathogenic | 0.5721 | pathogenic | 0.025 | Stabilizing | 1.0 | D | 0.527 | neutral | N | 0.494726505 | None | None | N |
| R/M | 0.7832 | likely_pathogenic | 0.6902 | pathogenic | -0.183 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| R/N | 0.9591 | likely_pathogenic | 0.9255 | pathogenic | -0.033 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | N |
| R/P | 0.9852 | likely_pathogenic | 0.9751 | pathogenic | -0.125 | Destabilizing | 1.0 | D | 0.625 | neutral | N | 0.495233484 | None | None | N |
| R/Q | 0.2672 | likely_benign | 0.2047 | benign | -0.274 | Destabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | N |
| R/S | 0.9318 | likely_pathogenic | 0.8809 | pathogenic | -0.635 | Destabilizing | 1.0 | D | 0.585 | neutral | N | 0.4686847 | None | None | N |
| R/T | 0.8954 | likely_pathogenic | 0.7987 | pathogenic | -0.438 | Destabilizing | 1.0 | D | 0.586 | neutral | None | None | None | None | N |
| R/V | 0.8731 | likely_pathogenic | 0.8178 | pathogenic | -0.125 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| R/W | 0.5027 | ambiguous | 0.422 | ambiguous | -0.58 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| R/Y | 0.8184 | likely_pathogenic | 0.7518 | pathogenic | -0.213 | Destabilizing | 1.0 | D | 0.667 | 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.