Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8025 | 24298;24299;24300 | chr2:178719317;178719316;178719315 | chr2:179584044;179584043;179584042 |
| N2AB | 7708 | 23347;23348;23349 | chr2:178719317;178719316;178719315 | chr2:179584044;179584043;179584042 |
| N2A | 6781 | 20566;20567;20568 | chr2:178719317;178719316;178719315 | chr2:179584044;179584043;179584042 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | rs1317114074  |
-1.065 | 0.497 | D | 0.434 | 0.376 | 0.499665682712 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 9.28E-05 | 0 | 0 |
| I/F | rs1317114074 |
-1.065 | 0.497 | D | 0.434 | 0.376 | 0.499665682712 | gnomAD-4.0.0 | 3.18242E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.76464E-05 | 0 | 0 | 0 | 0 |
| I/M | rs371496970 |
-0.336 | 0.497 | N | 0.462 | 0.304 | None | gnomAD-2.1.1 | 1.15724E-03 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.24776E-03 | None | 0 | 1.78E-05 | 4.96689E-04 |
| I/M | rs371496970 |
-0.336 | 0.497 | N | 0.462 | 0.304 | None | gnomAD-3.1.2 | 3.61852E-04 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 1.07705E-02 | 4.79386E-04 |
| I/M | rs371496970 |
-0.336 | 0.497 | N | 0.462 | 0.304 | None | 1000 genomes | 2.79553E-03 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1.43E-02 | None |
| I/M | rs371496970 |
-0.336 | 0.497 | N | 0.462 | 0.304 | None | gnomAD-4.0.0 | 5.98634E-04 | None | None | None | None | I | None | 0 | 1.66706E-05 | None | 0 | 0 | None | 0 | 3.30033E-04 | 4.2383E-06 | 1.00679E-02 | 6.56315E-04 |
| I/N | None | None | 0.859 | D | 0.695 | 0.596 | 0.89283046024 | gnomAD-4.0.0 | 1.59126E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02444E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2137 | likely_benign | 0.3274 | benign | -2.009 | Highly Destabilizing | 0.072 | N | 0.475 | neutral | None | None | None | None | I |
| I/C | 0.6462 | likely_pathogenic | 0.781 | pathogenic | -1.093 | Destabilizing | 0.909 | D | 0.525 | neutral | None | None | None | None | I |
| I/D | 0.7378 | likely_pathogenic | 0.8659 | pathogenic | -1.734 | Destabilizing | 0.726 | D | 0.692 | prob.neutral | None | None | None | None | I |
| I/E | 0.6072 | likely_pathogenic | 0.7737 | pathogenic | -1.565 | Destabilizing | 0.726 | D | 0.664 | neutral | None | None | None | None | I |
| I/F | 0.1378 | likely_benign | 0.1865 | benign | -1.175 | Destabilizing | 0.497 | N | 0.434 | neutral | D | 0.523857212 | None | None | I |
| I/G | 0.5919 | likely_pathogenic | 0.7633 | pathogenic | -2.494 | Highly Destabilizing | 0.726 | D | 0.655 | neutral | None | None | None | None | I |
| I/H | 0.5106 | ambiguous | 0.6742 | pathogenic | -1.816 | Destabilizing | 0.968 | D | 0.69 | prob.neutral | None | None | None | None | I |
| I/K | 0.401 | ambiguous | 0.5512 | ambiguous | -1.328 | Destabilizing | 0.726 | D | 0.658 | neutral | None | None | None | None | I |
| I/L | 0.0818 | likely_benign | 0.1053 | benign | -0.654 | Destabilizing | None | N | 0.131 | neutral | N | 0.452438316 | None | None | I |
| I/M | 0.0815 | likely_benign | 0.0985 | benign | -0.501 | Destabilizing | 0.497 | N | 0.462 | neutral | N | 0.505499467 | None | None | I |
| I/N | 0.3401 | ambiguous | 0.492 | ambiguous | -1.464 | Destabilizing | 0.859 | D | 0.695 | prob.neutral | D | 0.547748365 | None | None | I |
| I/P | 0.673 | likely_pathogenic | 0.8328 | pathogenic | -1.081 | Destabilizing | 0.726 | D | 0.698 | prob.neutral | None | None | None | None | I |
| I/Q | 0.4638 | ambiguous | 0.637 | pathogenic | -1.405 | Destabilizing | 0.89 | D | 0.693 | prob.neutral | None | None | None | None | I |
| I/R | 0.2873 | likely_benign | 0.4156 | ambiguous | -1.022 | Destabilizing | 0.726 | D | 0.695 | prob.neutral | None | None | None | None | I |
| I/S | 0.3213 | likely_benign | 0.4713 | ambiguous | -2.176 | Highly Destabilizing | 0.497 | N | 0.578 | neutral | D | 0.526503784 | None | None | I |
| I/T | 0.1595 | likely_benign | 0.2344 | benign | -1.865 | Destabilizing | 0.124 | N | 0.476 | neutral | D | 0.526348746 | None | None | I |
| I/V | 0.073 | likely_benign | 0.0887 | benign | -1.081 | Destabilizing | None | N | 0.133 | neutral | N | 0.511164119 | None | None | I |
| I/W | 0.6302 | likely_pathogenic | 0.7583 | pathogenic | -1.465 | Destabilizing | 0.968 | D | 0.709 | prob.delet. | None | None | None | None | I |
| I/Y | 0.4053 | ambiguous | 0.5254 | ambiguous | -1.143 | Destabilizing | 0.726 | D | 0.555 | neutral | 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.