Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14367 | 43324;43325;43326 | chr2:178633032;178633031;178633030 | chr2:179497759;179497758;179497757 |
| N2AB | 12726 | 38401;38402;38403 | chr2:178633032;178633031;178633030 | chr2:179497759;179497758;179497757 |
| N2A | 11799 | 35620;35621;35622 | chr2:178633032;178633031;178633030 | chr2:179497759;179497758;179497757 |
| N2B | 5302 | 16129;16130;16131 | chr2:178633032;178633031;178633030 | chr2:179497759;179497758;179497757 |
| Novex-1 | 5427 | 16504;16505;16506 | chr2:178633032;178633031;178633030 | chr2:179497759;179497758;179497757 |
| Novex-2 | 5494 | 16705;16706;16707 | chr2:178633032;178633031;178633030 | chr2:179497759;179497758;179497757 |
| 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/T | rs397517572  |
-3.166 | 0.915 | N | 0.392 | 0.218 | 0.518038692251 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 0 | 8.72E-05 | None | 0 | 5.62E-05 | None | 0 | None | 0 | 1.79E-05 | 0 |
| I/T | rs397517572 |
-3.166 | 0.915 | N | 0.392 | 0.218 | 0.518038692251 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs397517572 |
-3.166 | 0.915 | N | 0.392 | 0.218 | 0.518038692251 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/T | rs397517572 |
-3.166 | 0.915 | N | 0.392 | 0.218 | 0.518038692251 | gnomAD-4.0.0 | 3.78193E-05 | None | None | None | None | N | None | 0 | 1.16733E-04 | None | 0 | 2.23714E-05 | None | 0 | 0 | 4.15489E-05 | 2.19727E-05 | 3.20359E-05 |
| I/V | rs1243151462 |
-1.644 | 0.057 | N | 0.096 | 0.08 | 0.425028116352 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| I/V | rs1243151462 |
-1.644 | 0.057 | N | 0.096 | 0.08 | 0.425028116352 | gnomAD-4.0.0 | 5.47657E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29853E-06 | 1.16012E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.353 | ambiguous | 0.338 | benign | -1.728 | Destabilizing | 0.855 | D | 0.303 | neutral | None | None | None | None | N |
| I/C | 0.8152 | likely_pathogenic | 0.8142 | pathogenic | -0.843 | Destabilizing | 0.999 | D | 0.359 | neutral | None | None | None | None | N |
| I/D | 0.8312 | likely_pathogenic | 0.8123 | pathogenic | -1.568 | Destabilizing | 0.99 | D | 0.579 | neutral | None | None | None | None | N |
| I/E | 0.5741 | likely_pathogenic | 0.5474 | ambiguous | -1.58 | Destabilizing | 0.935 | D | 0.559 | neutral | None | None | None | None | N |
| I/F | 0.1971 | likely_benign | 0.1804 | benign | -1.275 | Destabilizing | 0.987 | D | 0.402 | neutral | N | 0.434315403 | None | None | N |
| I/G | 0.7932 | likely_pathogenic | 0.7733 | pathogenic | -2.036 | Highly Destabilizing | 0.967 | D | 0.578 | neutral | None | None | None | None | N |
| I/H | 0.4923 | ambiguous | 0.4545 | ambiguous | -1.331 | Destabilizing | 0.999 | D | 0.54 | neutral | None | None | None | None | N |
| I/K | 0.2724 | likely_benign | 0.2581 | benign | -1.361 | Destabilizing | 0.161 | N | 0.413 | neutral | None | None | None | None | N |
| I/L | 0.1675 | likely_benign | 0.1592 | benign | -0.949 | Destabilizing | 0.493 | N | 0.289 | neutral | N | 0.452533403 | None | None | N |
| I/M | 0.1226 | likely_benign | 0.1207 | benign | -0.617 | Destabilizing | 0.987 | D | 0.46 | neutral | N | 0.46116447 | None | None | N |
| I/N | 0.4174 | ambiguous | 0.3784 | ambiguous | -1.086 | Destabilizing | 0.987 | D | 0.615 | neutral | N | 0.422586193 | None | None | N |
| I/P | 0.9619 | likely_pathogenic | 0.9575 | pathogenic | -1.18 | Destabilizing | 0.997 | D | 0.613 | neutral | None | None | None | None | N |
| I/Q | 0.4131 | ambiguous | 0.3846 | ambiguous | -1.3 | Destabilizing | 0.98 | D | 0.641 | neutral | None | None | None | None | N |
| I/R | 0.1873 | likely_benign | 0.1786 | benign | -0.68 | Destabilizing | 0.962 | D | 0.573 | neutral | None | None | None | None | N |
| I/S | 0.3084 | likely_benign | 0.2993 | benign | -1.572 | Destabilizing | 0.915 | D | 0.465 | neutral | N | 0.429595178 | None | None | N |
| I/T | 0.1254 | likely_benign | 0.1201 | benign | -1.481 | Destabilizing | 0.915 | D | 0.392 | neutral | N | 0.429314234 | None | None | N |
| I/V | 0.1036 | likely_benign | 0.102 | benign | -1.18 | Destabilizing | 0.057 | N | 0.096 | neutral | N | 0.432696056 | None | None | N |
| I/W | 0.7448 | likely_pathogenic | 0.7213 | pathogenic | -1.382 | Destabilizing | 0.999 | D | 0.623 | neutral | None | None | None | None | N |
| I/Y | 0.5687 | likely_pathogenic | 0.5405 | ambiguous | -1.192 | Destabilizing | 0.997 | D | 0.448 | 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.