Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27782 | 83569;83570;83571 | chr2:178562788;178562787;178562786 | chr2:179427515;179427514;179427513 |
| N2AB | 26141 | 78646;78647;78648 | chr2:178562788;178562787;178562786 | chr2:179427515;179427514;179427513 |
| N2A | 25214 | 75865;75866;75867 | chr2:178562788;178562787;178562786 | chr2:179427515;179427514;179427513 |
| N2B | 18717 | 56374;56375;56376 | chr2:178562788;178562787;178562786 | chr2:179427515;179427514;179427513 |
| Novex-1 | 18842 | 56749;56750;56751 | chr2:178562788;178562787;178562786 | chr2:179427515;179427514;179427513 |
| Novex-2 | 18909 | 56950;56951;56952 | chr2:178562788;178562787;178562786 | chr2:179427515;179427514;179427513 |
| 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 | rs769862471  |
-0.29 | 0.221 | D | 0.535 | 0.337 | 0.511390160789 | 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 |
| S/L | rs769862471 |
-0.29 | 0.221 | D | 0.535 | 0.337 | 0.511390160789 | gnomAD-4.0.0 | 1.59248E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85941E-06 | 0 | 0 |
| S/P | None | None | 0.974 | D | 0.757 | 0.422 | 0.405700215632 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0805 | likely_benign | 0.0754 | benign | -0.901 | Destabilizing | 0.001 | N | 0.209 | neutral | N | 0.48206457 | None | None | N |
| S/C | 0.0837 | likely_benign | 0.0795 | benign | -1.111 | Destabilizing | 0.356 | N | 0.5 | neutral | None | None | None | None | N |
| S/D | 0.6867 | likely_pathogenic | 0.6556 | pathogenic | -1.936 | Destabilizing | 0.934 | D | 0.589 | neutral | None | None | None | None | N |
| S/E | 0.6964 | likely_pathogenic | 0.6826 | pathogenic | -1.8 | Destabilizing | 0.908 | D | 0.54 | neutral | None | None | None | None | N |
| S/F | 0.1645 | likely_benign | 0.1311 | benign | -0.755 | Destabilizing | 0.472 | N | 0.636 | neutral | None | None | None | None | N |
| S/G | 0.1313 | likely_benign | 0.1224 | benign | -1.223 | Destabilizing | 0.729 | D | 0.439 | neutral | None | None | None | None | N |
| S/H | 0.3582 | ambiguous | 0.3332 | benign | -1.494 | Destabilizing | 0.998 | D | 0.716 | prob.delet. | None | None | None | None | N |
| S/I | 0.2309 | likely_benign | 0.2196 | benign | -0.113 | Destabilizing | 0.993 | D | 0.635 | neutral | None | None | None | None | N |
| S/K | 0.8207 | likely_pathogenic | 0.8101 | pathogenic | -0.788 | Destabilizing | 0.999 | D | 0.529 | neutral | None | None | None | None | N |
| S/L | 0.1399 | likely_benign | 0.13 | benign | -0.113 | Destabilizing | 0.221 | N | 0.535 | neutral | D | 0.533378822 | None | None | N |
| S/M | 0.1766 | likely_benign | 0.1589 | benign | -0.217 | Destabilizing | 0.999 | D | 0.722 | prob.delet. | None | None | None | None | N |
| S/N | 0.2435 | likely_benign | 0.2384 | benign | -1.342 | Destabilizing | 0.625 | D | 0.576 | neutral | None | None | None | None | N |
| S/P | 0.9816 | likely_pathogenic | 0.9772 | pathogenic | -0.343 | Destabilizing | 0.974 | D | 0.757 | deleterious | D | 0.556256017 | None | None | N |
| S/Q | 0.5938 | likely_pathogenic | 0.5776 | pathogenic | -1.295 | Destabilizing | 0.995 | D | 0.622 | neutral | None | None | None | None | N |
| S/R | 0.7288 | likely_pathogenic | 0.7236 | pathogenic | -0.851 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| S/T | 0.0866 | likely_benign | 0.0815 | benign | -1.036 | Destabilizing | 0.04 | N | 0.431 | neutral | N | 0.484796367 | None | None | N |
| S/V | 0.2118 | likely_benign | 0.1964 | benign | -0.343 | Destabilizing | 0.957 | D | 0.577 | neutral | None | None | None | None | N |
| S/W | 0.3505 | ambiguous | 0.3199 | benign | -0.951 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| S/Y | 0.1866 | likely_benign | 0.1624 | benign | -0.559 | Destabilizing | 0.475 | N | 0.625 | 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.