Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23336 | 70231;70232;70233 | chr2:178576126;178576125;178576124 | chr2:179440853;179440852;179440851 |
| N2AB | 21695 | 65308;65309;65310 | chr2:178576126;178576125;178576124 | chr2:179440853;179440852;179440851 |
| N2A | 20768 | 62527;62528;62529 | chr2:178576126;178576125;178576124 | chr2:179440853;179440852;179440851 |
| N2B | 14271 | 43036;43037;43038 | chr2:178576126;178576125;178576124 | chr2:179440853;179440852;179440851 |
| Novex-1 | 14396 | 43411;43412;43413 | chr2:178576126;178576125;178576124 | chr2:179440853;179440852;179440851 |
| Novex-2 | 14463 | 43612;43613;43614 | chr2:178576126;178576125;178576124 | chr2:179440853;179440852;179440851 |
| 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/I | rs781015638  |
-0.6 | 0.008 | N | 0.299 | 0.093 | 0.299770980665 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 6.46E-05 | 2.9E-05 | None | 0 | 1.11894E-04 | None | 0 | None | 4.65E-05 | 0 | 0 |
| V/I | rs781015638 |
-0.6 | 0.008 | N | 0.299 | 0.093 | 0.299770980665 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs781015638 |
-0.6 | 0.008 | N | 0.299 | 0.093 | 0.299770980665 | gnomAD-4.0.0 | 1.05372E-05 | None | None | None | None | N | None | 5.3416E-05 | 0 | None | 0 | 4.46568E-05 | None | 0 | 0 | 8.47748E-06 | 0 | 1.60164E-05 |
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 | 0.1155 | likely_benign | 0.1171 | benign | -1.278 | Destabilizing | 0.163 | N | 0.486 | neutral | N | 0.478606197 | None | None | N |
| V/C | 0.5563 | ambiguous | 0.5713 | pathogenic | -0.989 | Destabilizing | 0.981 | D | 0.701 | prob.delet. | None | None | None | None | N |
| V/D | 0.3018 | likely_benign | 0.2999 | benign | -1.147 | Destabilizing | 0.687 | D | 0.799 | deleterious | None | None | None | None | N |
| V/E | 0.1639 | likely_benign | 0.1644 | benign | -1.207 | Destabilizing | 0.454 | N | 0.683 | prob.neutral | N | 0.500560337 | None | None | N |
| V/F | 0.1891 | likely_benign | 0.1922 | benign | -1.208 | Destabilizing | 0.687 | D | 0.668 | prob.neutral | None | None | None | None | N |
| V/G | 0.1842 | likely_benign | 0.1877 | benign | -1.514 | Destabilizing | 0.624 | D | 0.722 | deleterious | N | 0.500907053 | None | None | N |
| V/H | 0.3639 | ambiguous | 0.361 | ambiguous | -0.99 | Destabilizing | 0.981 | D | 0.818 | deleterious | None | None | None | None | N |
| V/I | 0.0741 | likely_benign | 0.0736 | benign | -0.759 | Destabilizing | 0.008 | N | 0.299 | neutral | N | 0.448630007 | None | None | N |
| V/K | 0.1393 | likely_benign | 0.1339 | benign | -0.989 | Destabilizing | 0.002 | N | 0.558 | neutral | None | None | None | None | N |
| V/L | 0.1316 | likely_benign | 0.1348 | benign | -0.759 | Destabilizing | 0.079 | N | 0.499 | neutral | N | 0.49813332 | None | None | N |
| V/M | 0.1046 | likely_benign | 0.1056 | benign | -0.558 | Destabilizing | 0.687 | D | 0.585 | neutral | None | None | None | None | N |
| V/N | 0.2007 | likely_benign | 0.1935 | benign | -0.758 | Destabilizing | 0.687 | D | 0.823 | deleterious | None | None | None | None | N |
| V/P | 0.7282 | likely_pathogenic | 0.7339 | pathogenic | -0.897 | Destabilizing | 0.817 | D | 0.767 | deleterious | None | None | None | None | N |
| V/Q | 0.1574 | likely_benign | 0.1535 | benign | -1.037 | Destabilizing | 0.687 | D | 0.758 | deleterious | None | None | None | None | N |
| V/R | 0.1478 | likely_benign | 0.1383 | benign | -0.402 | Destabilizing | 0.524 | D | 0.785 | deleterious | None | None | None | None | N |
| V/S | 0.1409 | likely_benign | 0.1398 | benign | -1.234 | Destabilizing | 0.687 | D | 0.677 | prob.neutral | None | None | None | None | N |
| V/T | 0.0935 | likely_benign | 0.0894 | benign | -1.195 | Destabilizing | 0.385 | N | 0.559 | neutral | None | None | None | None | N |
| V/W | 0.7378 | likely_pathogenic | 0.7561 | pathogenic | -1.288 | Destabilizing | 0.981 | D | 0.773 | deleterious | None | None | None | None | N |
| V/Y | 0.5005 | ambiguous | 0.5064 | ambiguous | -1.009 | Destabilizing | 0.817 | D | 0.682 | prob.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.