Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21193 | 63802;63803;63804 | chr2:178587732;178587731;178587730 | chr2:179452459;179452458;179452457 |
| N2AB | 19552 | 58879;58880;58881 | chr2:178587732;178587731;178587730 | chr2:179452459;179452458;179452457 |
| N2A | 18625 | 56098;56099;56100 | chr2:178587732;178587731;178587730 | chr2:179452459;179452458;179452457 |
| N2B | 12128 | 36607;36608;36609 | chr2:178587732;178587731;178587730 | chr2:179452459;179452458;179452457 |
| Novex-1 | 12253 | 36982;36983;36984 | chr2:178587732;178587731;178587730 | chr2:179452459;179452458;179452457 |
| Novex-2 | 12320 | 37183;37184;37185 | chr2:178587732;178587731;178587730 | chr2:179452459;179452458;179452457 |
| 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 | rs376800688  |
-0.594 | 1.0 | N | 0.739 | 0.366 | None | gnomAD-2.1.1 | 2.86899E-04 | None | None | None | None | I | None | 0 | 2.84E-05 | None | 0 | 0 | None | 0 | None | 4.02E-05 | 5.96556E-04 | 2.82566E-04 |
| R/C | rs376800688 |
-0.594 | 1.0 | N | 0.739 | 0.366 | None | gnomAD-3.1.2 | 3.35597E-04 | None | None | None | None | I | None | 1.69074E-04 | 3.93597E-04 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 5.44438E-04 | 0 | 0 |
| R/C | rs376800688 |
-0.594 | 1.0 | N | 0.739 | 0.366 | None | gnomAD-4.0.0 | 4.51428E-04 | None | None | None | None | I | None | 1.06732E-04 | 1.16799E-04 | None | 0 | 0 | None | 6.25508E-05 | 1.65399E-04 | 5.79169E-04 | 3.29736E-05 | 3.52429E-04 |
| R/H | rs372267046 |
-1.142 | 1.0 | N | 0.765 | 0.432 | None | gnomAD-2.1.1 | 7.89E-05 | None | None | None | None | I | None | 4.14E-05 | 8.52E-05 | None | 0 | 0 | None | 1.31027E-04 | None | 0 | 7.07E-05 | 7.06614E-04 |
| R/H | rs372267046 |
-1.142 | 1.0 | N | 0.765 | 0.432 | None | gnomAD-3.1.2 | 7.24E-05 | None | None | None | None | I | None | 7.25E-05 | 2.62433E-04 | 0 | 0 | 1.94401E-04 | None | 0 | 0 | 2.94E-05 | 0 | 4.78927E-04 |
| R/H | rs372267046 |
-1.142 | 1.0 | N | 0.765 | 0.432 | None | gnomAD-4.0.0 | 9.1164E-05 | None | None | None | None | I | None | 5.34559E-05 | 1.00164E-04 | None | 0 | 2.23964E-05 | None | 0 | 8.23995E-04 | 9.66716E-05 | 1.20892E-04 | 9.61508E-05 |
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 | 0.9626 | likely_pathogenic | 0.9506 | pathogenic | -0.289 | Destabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | I |
| R/C | 0.6461 | likely_pathogenic | 0.5574 | ambiguous | -0.528 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.498092369 | None | None | I |
| R/D | 0.9829 | likely_pathogenic | 0.9771 | pathogenic | 0.036 | Stabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| R/E | 0.9073 | likely_pathogenic | 0.8718 | pathogenic | 0.151 | Stabilizing | 0.999 | D | 0.65 | neutral | None | None | None | None | I |
| R/F | 0.9635 | likely_pathogenic | 0.9476 | pathogenic | -0.3 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| R/G | 0.9361 | likely_pathogenic | 0.9157 | pathogenic | -0.548 | Destabilizing | 1.0 | D | 0.663 | neutral | N | 0.509195185 | None | None | I |
| R/H | 0.3722 | ambiguous | 0.3043 | benign | -0.919 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.480290829 | None | None | I |
| R/I | 0.8959 | likely_pathogenic | 0.8426 | pathogenic | 0.382 | Stabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| R/K | 0.538 | ambiguous | 0.4606 | ambiguous | -0.284 | Destabilizing | 0.998 | D | 0.53 | neutral | None | None | None | None | I |
| R/L | 0.8182 | likely_pathogenic | 0.7689 | pathogenic | 0.382 | Stabilizing | 1.0 | D | 0.663 | neutral | N | 0.477453219 | None | None | I |
| R/M | 0.915 | likely_pathogenic | 0.8658 | pathogenic | -0.187 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| R/N | 0.9634 | likely_pathogenic | 0.9477 | pathogenic | -0.157 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| R/P | 0.9802 | likely_pathogenic | 0.9753 | pathogenic | 0.179 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | N | 0.52055149 | None | None | I |
| R/Q | 0.3999 | ambiguous | 0.3297 | benign | -0.192 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| R/S | 0.9463 | likely_pathogenic | 0.931 | pathogenic | -0.677 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | N | 0.457969839 | None | None | I |
| R/T | 0.8906 | likely_pathogenic | 0.8368 | pathogenic | -0.39 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| R/V | 0.9049 | likely_pathogenic | 0.8728 | pathogenic | 0.179 | Stabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| R/W | 0.6708 | likely_pathogenic | 0.5805 | pathogenic | -0.208 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| R/Y | 0.8888 | likely_pathogenic | 0.8423 | pathogenic | 0.159 | Stabilizing | 1.0 | D | 0.741 | deleterious | None | None | 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.