Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7130 | 21613;21614;21615 | chr2:178723871;178723870;178723869 | chr2:179588598;179588597;179588596 |
| N2AB | 6813 | 20662;20663;20664 | chr2:178723871;178723870;178723869 | chr2:179588598;179588597;179588596 |
| N2A | 5886 | 17881;17882;17883 | chr2:178723871;178723870;178723869 | chr2:179588598;179588597;179588596 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs373905235  |
-0.385 | None | N | 0.113 | 0.075 | 0.143124449307 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| V/L | rs373905235 |
-0.385 | None | N | 0.113 | 0.075 | 0.143124449307 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/L | rs373905235 |
-0.385 | None | N | 0.113 | 0.075 | 0.143124449307 | gnomAD-4.0.0 | 2.48313E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39586E-06 | 0 | 0 |
| V/M | None | None | 0.002 | N | 0.255 | 0.158 | 0.166414681773 | gnomAD-4.0.0 | 6.85555E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.01E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0776 | likely_benign | 0.1019 | benign | -1.082 | Destabilizing | None | N | 0.112 | neutral | N | 0.473701809 | None | None | N |
| V/C | 0.5444 | ambiguous | 0.5759 | pathogenic | -0.877 | Destabilizing | 0.356 | N | 0.536 | neutral | None | None | None | None | N |
| V/D | 0.124 | likely_benign | 0.1388 | benign | -0.741 | Destabilizing | 0.038 | N | 0.567 | neutral | None | None | None | None | N |
| V/E | 0.113 | likely_benign | 0.1216 | benign | -0.818 | Destabilizing | 0.012 | N | 0.501 | neutral | N | 0.46517554 | None | None | N |
| V/F | 0.081 | likely_benign | 0.0817 | benign | -1.193 | Destabilizing | 0.038 | N | 0.599 | neutral | None | None | None | None | N |
| V/G | 0.1125 | likely_benign | 0.1245 | benign | -1.291 | Destabilizing | 0.012 | N | 0.477 | neutral | D | 0.528805731 | None | None | N |
| V/H | 0.2568 | likely_benign | 0.2672 | benign | -0.833 | Destabilizing | 0.356 | N | 0.599 | neutral | None | None | None | None | N |
| V/I | 0.0683 | likely_benign | 0.0721 | benign | -0.649 | Destabilizing | None | N | 0.078 | neutral | None | None | None | None | N |
| V/K | 0.1583 | likely_benign | 0.1648 | benign | -0.709 | Destabilizing | None | N | 0.283 | neutral | None | None | None | None | N |
| V/L | 0.093 | likely_benign | 0.1011 | benign | -0.649 | Destabilizing | None | N | 0.113 | neutral | N | 0.472432373 | None | None | N |
| V/M | 0.0831 | likely_benign | 0.091 | benign | -0.458 | Destabilizing | 0.002 | N | 0.255 | neutral | N | 0.512721557 | None | None | N |
| V/N | 0.1114 | likely_benign | 0.1227 | benign | -0.464 | Destabilizing | None | N | 0.349 | neutral | None | None | None | None | N |
| V/P | 0.256 | likely_benign | 0.2837 | benign | -0.758 | Destabilizing | 0.072 | N | 0.644 | neutral | None | None | None | None | N |
| V/Q | 0.143 | likely_benign | 0.1483 | benign | -0.743 | Destabilizing | 0.038 | N | 0.652 | neutral | None | None | None | None | N |
| V/R | 0.1329 | likely_benign | 0.1355 | benign | -0.176 | Destabilizing | 0.038 | N | 0.623 | neutral | None | None | None | None | N |
| V/S | 0.0861 | likely_benign | 0.0974 | benign | -0.946 | Destabilizing | 0.016 | N | 0.409 | neutral | None | None | None | None | N |
| V/T | 0.0942 | likely_benign | 0.1053 | benign | -0.919 | Destabilizing | None | N | 0.09 | neutral | None | None | None | None | N |
| V/W | 0.4484 | ambiguous | 0.479 | ambiguous | -1.256 | Destabilizing | 0.864 | D | 0.599 | neutral | None | None | None | None | N |
| V/Y | 0.2662 | likely_benign | 0.2789 | benign | -0.942 | Destabilizing | 0.356 | N | 0.589 | 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.