Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23149 | 69670;69671;69672 | chr2:178576799;178576798;178576797 | chr2:179441526;179441525;179441524 |
| N2AB | 21508 | 64747;64748;64749 | chr2:178576799;178576798;178576797 | chr2:179441526;179441525;179441524 |
| N2A | 20581 | 61966;61967;61968 | chr2:178576799;178576798;178576797 | chr2:179441526;179441525;179441524 |
| N2B | 14084 | 42475;42476;42477 | chr2:178576799;178576798;178576797 | chr2:179441526;179441525;179441524 |
| Novex-1 | 14209 | 42850;42851;42852 | chr2:178576799;178576798;178576797 | chr2:179441526;179441525;179441524 |
| Novex-2 | 14276 | 43051;43052;43053 | chr2:178576799;178576798;178576797 | chr2:179441526;179441525;179441524 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/L | rs1559465254  |
None | 0.326 | N | 0.447 | 0.278 | 0.422883881359 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 0 |
| S/L | rs1559465254 |
None | 0.326 | N | 0.447 | 0.278 | 0.422883881359 | gnomAD-4.0.0 | 1.59269E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77762E-05 | None | 0 | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1032 | likely_benign | 0.1014 | benign | -0.36 | Destabilizing | 0.08 | N | 0.229 | neutral | N | 0.465804684 | None | None | N |
| S/C | 0.1096 | likely_benign | 0.1144 | benign | -0.263 | Destabilizing | 0.991 | D | 0.438 | neutral | None | None | None | None | N |
| S/D | 0.4831 | ambiguous | 0.5014 | ambiguous | 0.012 | Stabilizing | 0.001 | N | 0.075 | neutral | None | None | None | None | N |
| S/E | 0.5884 | likely_pathogenic | 0.5921 | pathogenic | -0.09 | Destabilizing | 0.209 | N | 0.343 | neutral | None | None | None | None | N |
| S/F | 0.1995 | likely_benign | 0.1919 | benign | -1.013 | Destabilizing | 0.901 | D | 0.507 | neutral | None | None | None | None | N |
| S/G | 0.1129 | likely_benign | 0.1087 | benign | -0.453 | Destabilizing | 0.345 | N | 0.346 | neutral | None | None | None | None | N |
| S/H | 0.3577 | ambiguous | 0.3611 | ambiguous | -1.01 | Destabilizing | 0.965 | D | 0.447 | neutral | None | None | None | None | N |
| S/I | 0.164 | likely_benign | 0.1726 | benign | -0.245 | Destabilizing | 0.561 | D | 0.507 | neutral | None | None | None | None | N |
| S/K | 0.6912 | likely_pathogenic | 0.6912 | pathogenic | -0.467 | Destabilizing | 0.561 | D | 0.318 | neutral | None | None | None | None | N |
| S/L | 0.1073 | likely_benign | 0.1037 | benign | -0.245 | Destabilizing | 0.326 | N | 0.447 | neutral | N | 0.432230828 | None | None | N |
| S/M | 0.1752 | likely_benign | 0.1758 | benign | 0.058 | Stabilizing | 0.965 | D | 0.447 | neutral | None | None | None | None | N |
| S/N | 0.1517 | likely_benign | 0.163 | benign | -0.201 | Destabilizing | 0.345 | N | 0.366 | neutral | None | None | None | None | N |
| S/P | 0.8523 | likely_pathogenic | 0.8405 | pathogenic | -0.256 | Destabilizing | 0.662 | D | 0.474 | neutral | D | 0.526199782 | None | None | N |
| S/Q | 0.503 | ambiguous | 0.5087 | ambiguous | -0.481 | Destabilizing | 0.722 | D | 0.414 | neutral | None | None | None | None | N |
| S/R | 0.6166 | likely_pathogenic | 0.6235 | pathogenic | -0.255 | Destabilizing | 0.561 | D | 0.499 | neutral | None | None | None | None | N |
| S/T | 0.0662 | likely_benign | 0.0652 | benign | -0.296 | Destabilizing | None | N | 0.079 | neutral | N | 0.417317304 | None | None | N |
| S/V | 0.1624 | likely_benign | 0.1653 | benign | -0.256 | Destabilizing | 0.39 | N | 0.443 | neutral | None | None | None | None | N |
| S/W | 0.3296 | likely_benign | 0.3239 | benign | -1.024 | Destabilizing | 0.991 | D | 0.509 | neutral | None | None | None | None | N |
| S/Y | 0.2108 | likely_benign | 0.2014 | benign | -0.739 | Destabilizing | 0.965 | D | 0.494 | 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.