Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15040 | 45343;45344;45345 | chr2:178621706;178621705;178621704 | chr2:179486433;179486432;179486431 |
| N2AB | 13399 | 40420;40421;40422 | chr2:178621706;178621705;178621704 | chr2:179486433;179486432;179486431 |
| N2A | 12472 | 37639;37640;37641 | chr2:178621706;178621705;178621704 | chr2:179486433;179486432;179486431 |
| N2B | 5975 | 18148;18149;18150 | chr2:178621706;178621705;178621704 | chr2:179486433;179486432;179486431 |
| Novex-1 | 6100 | 18523;18524;18525 | chr2:178621706;178621705;178621704 | chr2:179486433;179486432;179486431 |
| Novex-2 | 6167 | 18724;18725;18726 | chr2:178621706;178621705;178621704 | chr2:179486433;179486432;179486431 |
| 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/M | rs74580375  |
-0.647 | 0.188 | N | 0.539 | 0.042 | None | gnomAD-2.1.1 | 1.07626E-03 | None | None | None | None | N | None | 1.66044E-04 | 0 | None | 0 | 1.42051E-02 | None | 5.57706E-04 | None | 0 | 1.59E-05 | 4.26743E-04 |
| I/M | rs74580375 |
-0.647 | 0.188 | N | 0.539 | 0.042 | None | gnomAD-3.1.2 | 6.32053E-04 | None | None | None | None | N | None | 7.24E-05 | 1.3132E-04 | 0 | 0 | 1.5181E-02 | None | 0 | 0 | 4.42E-05 | 2.07211E-03 | 0 |
| I/M | rs74580375 |
-0.647 | 0.188 | N | 0.539 | 0.042 | None | 1000 genomes | 3.79393E-03 | None | None | None | None | N | None | 0 | 0 | None | None | 1.59E-02 | 0 | None | None | None | 3.1E-03 | None |
| I/M | rs74580375 |
-0.647 | 0.188 | N | 0.539 | 0.042 | None | gnomAD-4.0.0 | 3.92098E-04 | None | None | None | None | N | None | 8.00876E-05 | 5.01689E-05 | None | 0 | 1.08159E-02 | None | 0 | 0 | 2.03577E-05 | 7.03668E-04 | 8.49986E-04 |
| I/T | rs1334750715 |
None | 0.117 | N | 0.506 | 0.201 | 0.592052101994 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 1.94932E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1334750715 |
None | 0.117 | N | 0.506 | 0.201 | 0.592052101994 | gnomAD-4.0.0 | 2.48169E-06 | None | None | None | None | N | None | 1.33518E-05 | 0 | None | 0 | 2.24437E-05 | None | 0 | 0 | 0 | 1.09953E-05 | 1.60385E-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 | 0.1262 | likely_benign | 0.1883 | benign | -1.459 | Destabilizing | 0.035 | N | 0.419 | neutral | None | None | None | None | N |
| I/C | 0.5865 | likely_pathogenic | 0.6741 | pathogenic | -0.989 | Destabilizing | 0.824 | D | 0.517 | neutral | None | None | None | None | N |
| I/D | 0.4162 | ambiguous | 0.6508 | pathogenic | -0.914 | Destabilizing | 0.38 | N | 0.602 | neutral | None | None | None | None | N |
| I/E | 0.304 | likely_benign | 0.4565 | ambiguous | -0.908 | Destabilizing | 0.081 | N | 0.59 | neutral | None | None | None | None | N |
| I/F | 0.1376 | likely_benign | 0.1648 | benign | -0.961 | Destabilizing | 0.188 | N | 0.545 | neutral | N | 0.505141026 | None | None | N |
| I/G | 0.347 | ambiguous | 0.5541 | ambiguous | -1.784 | Destabilizing | 0.262 | N | 0.583 | neutral | None | None | None | None | N |
| I/H | 0.3597 | ambiguous | 0.4732 | ambiguous | -1.038 | Destabilizing | 0.824 | D | 0.579 | neutral | None | None | None | None | N |
| I/K | 0.2062 | likely_benign | 0.297 | benign | -1.097 | Destabilizing | 0.081 | N | 0.583 | neutral | None | None | None | None | N |
| I/L | 0.1012 | likely_benign | 0.1126 | benign | -0.647 | Destabilizing | None | N | 0.107 | neutral | N | 0.422409905 | None | None | N |
| I/M | 0.0789 | likely_benign | 0.0732 | benign | -0.594 | Destabilizing | 0.188 | N | 0.539 | neutral | N | 0.514196798 | None | None | N |
| I/N | 0.1681 | likely_benign | 0.2841 | benign | -0.92 | Destabilizing | 0.484 | N | 0.598 | neutral | N | 0.510963492 | None | None | N |
| I/P | 0.7038 | likely_pathogenic | 0.8584 | pathogenic | -0.886 | Destabilizing | 0.791 | D | 0.598 | neutral | None | None | None | None | N |
| I/Q | 0.2395 | likely_benign | 0.3471 | ambiguous | -1.058 | Destabilizing | 0.016 | N | 0.383 | neutral | None | None | None | None | N |
| I/R | 0.1582 | likely_benign | 0.22 | benign | -0.555 | Destabilizing | 0.38 | N | 0.596 | neutral | None | None | None | None | N |
| I/S | 0.1514 | likely_benign | 0.2226 | benign | -1.505 | Destabilizing | 0.117 | N | 0.543 | neutral | N | 0.514798211 | None | None | N |
| I/T | 0.0785 | likely_benign | 0.0889 | benign | -1.375 | Destabilizing | 0.117 | N | 0.506 | neutral | N | 0.502725813 | None | None | N |
| I/V | 0.0593 | likely_benign | 0.0653 | benign | -0.886 | Destabilizing | None | N | 0.106 | neutral | N | 0.423174297 | None | None | N |
| I/W | 0.6305 | likely_pathogenic | 0.6975 | pathogenic | -1.045 | Destabilizing | 0.935 | D | 0.6 | neutral | None | None | None | None | N |
| I/Y | 0.4036 | ambiguous | 0.517 | ambiguous | -0.82 | Destabilizing | 0.555 | D | 0.556 | 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.