Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22129 | 66610;66611;66612 | chr2:178581984;178581983;178581982 | chr2:179446711;179446710;179446709 |
| N2AB | 20488 | 61687;61688;61689 | chr2:178581984;178581983;178581982 | chr2:179446711;179446710;179446709 |
| N2A | 19561 | 58906;58907;58908 | chr2:178581984;178581983;178581982 | chr2:179446711;179446710;179446709 |
| N2B | 13064 | 39415;39416;39417 | chr2:178581984;178581983;178581982 | chr2:179446711;179446710;179446709 |
| Novex-1 | 13189 | 39790;39791;39792 | chr2:178581984;178581983;178581982 | chr2:179446711;179446710;179446709 |
| Novex-2 | 13256 | 39991;39992;39993 | chr2:178581984;178581983;178581982 | chr2:179446711;179446710;179446709 |
| 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 | rs763729258  |
-1.516 | 1.0 | D | 0.769 | 0.538 | 0.582480569846 | gnomAD-2.1.1 | 1.12691E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 8.49784E-04 | None | 0 | 8.89E-06 | 0 |
| R/C | rs763729258 |
-1.516 | 1.0 | D | 0.769 | 0.538 | 0.582480569846 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 8.28844E-04 | 0 |
| R/C | rs763729258 |
-1.516 | 1.0 | D | 0.769 | 0.538 | 0.582480569846 | gnomAD-4.0.0 | 4.89732E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.23404E-05 | None | 0 | 0 | 5.08683E-06 | 7.46695E-04 | 6.40738E-05 |
| R/H | rs187257105 |
-2.132 | 1.0 | D | 0.815 | 0.609 | None | gnomAD-2.1.1 | 1.57232E-04 | None | None | None | None | N | None | 4.13E-05 | 2.83E-05 | None | 0 | 0 | None | 1.07843E-03 | None | 0 | 6.26E-05 | 1.40607E-04 |
| R/H | rs187257105 |
-2.132 | 1.0 | D | 0.815 | 0.609 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 4.83E-05 | 6.56E-05 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 1.47E-05 | 6.21633E-04 | 0 |
| R/H | rs187257105 |
-2.132 | 1.0 | D | 0.815 | 0.609 | None | gnomAD-4.0.0 | 5.88866E-05 | None | None | None | None | N | None | 4.0016E-05 | 3.33522E-05 | None | 0 | 0 | None | 3.12461E-05 | 0 | 1.44128E-05 | 7.35714E-04 | 6.40471E-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 | 0.9727 | likely_pathogenic | 0.9716 | pathogenic | -1.811 | Destabilizing | 0.999 | D | 0.644 | neutral | None | None | None | None | N |
| R/C | 0.5256 | ambiguous | 0.5577 | ambiguous | -1.797 | Destabilizing | 1.0 | D | 0.769 | deleterious | D | 0.535968807 | None | None | N |
| R/D | 0.9982 | likely_pathogenic | 0.9981 | pathogenic | -0.792 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| R/E | 0.9636 | likely_pathogenic | 0.9632 | pathogenic | -0.585 | Destabilizing | 0.999 | D | 0.696 | prob.neutral | None | None | None | None | N |
| R/F | 0.9741 | likely_pathogenic | 0.976 | pathogenic | -1.098 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| R/G | 0.9814 | likely_pathogenic | 0.9793 | pathogenic | -2.161 | Highly Destabilizing | 1.0 | D | 0.734 | prob.delet. | D | 0.553819572 | None | None | N |
| R/H | 0.3071 | likely_benign | 0.3503 | ambiguous | -2.034 | Highly Destabilizing | 1.0 | D | 0.815 | deleterious | D | 0.542716757 | None | None | N |
| R/I | 0.9248 | likely_pathogenic | 0.926 | pathogenic | -0.807 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| R/K | 0.479 | ambiguous | 0.505 | ambiguous | -1.34 | Destabilizing | 0.998 | D | 0.665 | neutral | None | None | None | None | N |
| R/L | 0.8929 | likely_pathogenic | 0.8883 | pathogenic | -0.807 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | D | 0.527575016 | None | None | N |
| R/M | 0.9337 | likely_pathogenic | 0.9366 | pathogenic | -1.316 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| R/N | 0.9881 | likely_pathogenic | 0.9897 | pathogenic | -1.217 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | N |
| R/P | 0.9995 | likely_pathogenic | 0.9994 | pathogenic | -1.129 | Destabilizing | 1.0 | D | 0.775 | deleterious | D | 0.554326551 | None | None | N |
| R/Q | 0.3677 | ambiguous | 0.3849 | ambiguous | -1.128 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| R/S | 0.9825 | likely_pathogenic | 0.9826 | pathogenic | -2.122 | Highly Destabilizing | 1.0 | D | 0.749 | deleterious | N | 0.509707343 | None | None | N |
| R/T | 0.9702 | likely_pathogenic | 0.9665 | pathogenic | -1.704 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| R/V | 0.939 | likely_pathogenic | 0.9412 | pathogenic | -1.129 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| R/W | 0.7643 | likely_pathogenic | 0.746 | pathogenic | -0.612 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| R/Y | 0.9343 | likely_pathogenic | 0.9404 | pathogenic | -0.442 | Destabilizing | 1.0 | D | 0.801 | deleterious | 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.