Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20134 | 60625;60626;60627 | chr2:178591325;178591324;178591323 | chr2:179456052;179456051;179456050 |
| N2AB | 18493 | 55702;55703;55704 | chr2:178591325;178591324;178591323 | chr2:179456052;179456051;179456050 |
| N2A | 17566 | 52921;52922;52923 | chr2:178591325;178591324;178591323 | chr2:179456052;179456051;179456050 |
| N2B | 11069 | 33430;33431;33432 | chr2:178591325;178591324;178591323 | chr2:179456052;179456051;179456050 |
| Novex-1 | 11194 | 33805;33806;33807 | chr2:178591325;178591324;178591323 | chr2:179456052;179456051;179456050 |
| Novex-2 | 11261 | 34006;34007;34008 | chr2:178591325;178591324;178591323 | chr2:179456052;179456051;179456050 |
| 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 | None | None | 0.454 | N | 0.72 | 0.431 | 0.428747304603 | 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 |
| S/T | rs904878126  |
-0.148 | 0.007 | N | 0.345 | 0.111 | 0.149567049428 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 8.69E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/T | rs904878126 |
-0.148 | 0.007 | N | 0.345 | 0.111 | 0.149567049428 | gnomAD-4.0.0 | 4.77652E-06 | None | None | None | None | N | None | 0 | 6.86028E-05 | None | 0 | 0 | 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 | 0.1147 | likely_benign | 0.1141 | benign | -0.882 | Destabilizing | 0.267 | N | 0.519 | neutral | N | 0.508021374 | None | None | N |
| S/C | 0.1433 | likely_benign | 0.1489 | benign | -0.656 | Destabilizing | 0.998 | D | 0.763 | deleterious | None | None | None | None | N |
| S/D | 0.975 | likely_pathogenic | 0.9791 | pathogenic | -1.388 | Destabilizing | 0.842 | D | 0.709 | prob.delet. | None | None | None | None | N |
| S/E | 0.9853 | likely_pathogenic | 0.9885 | pathogenic | -1.2 | Destabilizing | 0.842 | D | 0.705 | prob.neutral | None | None | None | None | N |
| S/F | 0.8931 | likely_pathogenic | 0.8974 | pathogenic | -0.831 | Destabilizing | 0.974 | D | 0.819 | deleterious | None | None | None | None | N |
| S/G | 0.324 | likely_benign | 0.3281 | benign | -1.264 | Destabilizing | 0.688 | D | 0.687 | prob.neutral | None | None | None | None | N |
| S/H | 0.9335 | likely_pathogenic | 0.9429 | pathogenic | -1.635 | Destabilizing | 0.991 | D | 0.765 | deleterious | None | None | None | None | N |
| S/I | 0.6745 | likely_pathogenic | 0.6985 | pathogenic | 0.088 | Stabilizing | 0.842 | D | 0.781 | deleterious | None | None | None | None | N |
| S/K | 0.9963 | likely_pathogenic | 0.9972 | pathogenic | -0.123 | Destabilizing | 0.842 | D | 0.709 | prob.delet. | None | None | None | None | N |
| S/L | 0.4234 | ambiguous | 0.4362 | ambiguous | 0.088 | Stabilizing | 0.454 | N | 0.72 | prob.delet. | N | 0.462844911 | None | None | N |
| S/M | 0.5349 | ambiguous | 0.5345 | ambiguous | 0.035 | Stabilizing | 0.991 | D | 0.771 | deleterious | None | None | None | None | N |
| S/N | 0.7827 | likely_pathogenic | 0.8161 | pathogenic | -0.814 | Destabilizing | 0.842 | D | 0.688 | prob.neutral | None | None | None | None | N |
| S/P | 0.9864 | likely_pathogenic | 0.9887 | pathogenic | -0.202 | Destabilizing | 0.891 | D | 0.782 | deleterious | N | 0.46924092 | None | None | N |
| S/Q | 0.972 | likely_pathogenic | 0.9748 | pathogenic | -0.612 | Destabilizing | 0.974 | D | 0.778 | deleterious | None | None | None | None | N |
| S/R | 0.9926 | likely_pathogenic | 0.994 | pathogenic | -0.516 | Destabilizing | 0.842 | D | 0.799 | deleterious | None | None | None | None | N |
| S/T | 0.0754 | likely_benign | 0.0817 | benign | -0.509 | Destabilizing | 0.007 | N | 0.345 | neutral | N | 0.430792741 | None | None | N |
| S/V | 0.4588 | ambiguous | 0.4839 | ambiguous | -0.202 | Destabilizing | 0.525 | D | 0.72 | prob.delet. | None | None | None | None | N |
| S/W | 0.9512 | likely_pathogenic | 0.9509 | pathogenic | -1.052 | Destabilizing | 0.998 | D | 0.783 | deleterious | None | None | None | None | N |
| S/Y | 0.8669 | likely_pathogenic | 0.8777 | pathogenic | -0.601 | Destabilizing | 0.991 | D | 0.817 | 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.