Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26953 | 81082;81083;81084 | chr2:178565275;178565274;178565273 | chr2:179430002;179430001;179430000 |
| N2AB | 25312 | 76159;76160;76161 | chr2:178565275;178565274;178565273 | chr2:179430002;179430001;179430000 |
| N2A | 24385 | 73378;73379;73380 | chr2:178565275;178565274;178565273 | chr2:179430002;179430001;179430000 |
| N2B | 17888 | 53887;53888;53889 | chr2:178565275;178565274;178565273 | chr2:179430002;179430001;179430000 |
| Novex-1 | 18013 | 54262;54263;54264 | chr2:178565275;178565274;178565273 | chr2:179430002;179430001;179430000 |
| Novex-2 | 18080 | 54463;54464;54465 | chr2:178565275;178565274;178565273 | chr2:179430002;179430001;179430000 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/M | rs377506142  |
0.069 | 0.509 | N | 0.507 | 0.301 | 0.594056560588 | gnomAD-2.1.1 | 8.19021E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 7.15827E-03 | None | 0 | 2.35E-05 | 9.83146E-04 |
| T/M | rs377506142 |
0.069 | 0.509 | N | 0.507 | 0.301 | 0.594056560588 | gnomAD-3.1.2 | 2.43367E-04 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 1.93274E-04 | None | 0 | 0 | 1.47E-05 | 7.04225E-03 | 0 |
| T/M | rs377506142 |
0.069 | 0.509 | N | 0.507 | 0.301 | 0.594056560588 | 1000 genomes | 1.59744E-03 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 8.2E-03 | None |
| T/M | rs377506142 |
0.069 | 0.509 | N | 0.507 | 0.301 | 0.594056560588 | gnomAD-4.0.0 | 4.00976E-04 | None | None | None | None | N | None | 3.99989E-05 | 0 | None | 0 | 2.23045E-05 | None | 0 | 0 | 1.18677E-05 | 6.56623E-03 | 4.96318E-04 |
| T/R | rs377506142 |
-0.048 | 0.959 | D | 0.731 | 0.441 | 0.650727440417 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| T/R | rs377506142 |
-0.048 | 0.959 | D | 0.731 | 0.441 | 0.650727440417 | gnomAD-4.0.0 | 3.42134E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49768E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0934 | likely_benign | 0.0945 | benign | -1.098 | Destabilizing | 0.565 | D | 0.579 | neutral | N | 0.488694978 | None | None | N |
| T/C | 0.3414 | ambiguous | 0.3287 | benign | -0.892 | Destabilizing | 0.996 | D | 0.707 | prob.neutral | None | None | None | None | N |
| T/D | 0.5906 | likely_pathogenic | 0.5822 | pathogenic | -1.065 | Destabilizing | 0.923 | D | 0.696 | prob.neutral | None | None | None | None | N |
| T/E | 0.3234 | likely_benign | 0.3343 | benign | -0.981 | Destabilizing | 0.923 | D | 0.692 | prob.neutral | None | None | None | None | N |
| T/F | 0.2167 | likely_benign | 0.2069 | benign | -1.016 | Destabilizing | 0.923 | D | 0.79 | deleterious | None | None | None | None | N |
| T/G | 0.3665 | ambiguous | 0.353 | ambiguous | -1.422 | Destabilizing | 0.775 | D | 0.724 | prob.delet. | None | None | None | None | N |
| T/H | 0.2302 | likely_benign | 0.2198 | benign | -1.644 | Destabilizing | 0.054 | N | 0.557 | neutral | None | None | None | None | N |
| T/I | 0.128 | likely_benign | 0.1203 | benign | -0.294 | Destabilizing | 0.858 | D | 0.695 | prob.neutral | None | None | None | None | N |
| T/K | 0.1708 | likely_benign | 0.1647 | benign | -0.775 | Destabilizing | 0.959 | D | 0.689 | prob.neutral | N | 0.502984566 | None | None | N |
| T/L | 0.1 | likely_benign | 0.0965 | benign | -0.294 | Destabilizing | 0.372 | N | 0.637 | neutral | None | None | None | None | N |
| T/M | 0.0815 | likely_benign | 0.0801 | benign | -0.086 | Destabilizing | 0.509 | D | 0.507 | neutral | N | 0.498938874 | None | None | N |
| T/N | 0.1775 | likely_benign | 0.1709 | benign | -1.06 | Destabilizing | 0.923 | D | 0.613 | neutral | None | None | None | None | N |
| T/P | 0.7478 | likely_pathogenic | 0.7301 | pathogenic | -0.53 | Destabilizing | 0.983 | D | 0.737 | prob.delet. | D | 0.542389086 | None | None | N |
| T/Q | 0.2055 | likely_benign | 0.2013 | benign | -1.145 | Destabilizing | 0.923 | D | 0.737 | prob.delet. | None | None | None | None | N |
| T/R | 0.1372 | likely_benign | 0.132 | benign | -0.652 | Destabilizing | 0.959 | D | 0.731 | prob.delet. | D | 0.53319283 | None | None | N |
| T/S | 0.1293 | likely_benign | 0.1243 | benign | -1.318 | Destabilizing | 0.722 | D | 0.588 | neutral | N | 0.507489096 | None | None | N |
| T/V | 0.115 | likely_benign | 0.1096 | benign | -0.53 | Destabilizing | 0.633 | D | 0.582 | neutral | None | None | None | None | N |
| T/W | 0.586 | likely_pathogenic | 0.5711 | pathogenic | -0.991 | Destabilizing | 0.996 | D | 0.789 | deleterious | None | None | None | None | N |
| T/Y | 0.261 | likely_benign | 0.2471 | benign | -0.698 | Destabilizing | 0.923 | D | 0.789 | deleterious | 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.