Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26758 | 80497;80498;80499 | chr2:178565860;178565859;178565858 | chr2:179430587;179430586;179430585 |
| N2AB | 25117 | 75574;75575;75576 | chr2:178565860;178565859;178565858 | chr2:179430587;179430586;179430585 |
| N2A | 24190 | 72793;72794;72795 | chr2:178565860;178565859;178565858 | chr2:179430587;179430586;179430585 |
| N2B | 17693 | 53302;53303;53304 | chr2:178565860;178565859;178565858 | chr2:179430587;179430586;179430585 |
| Novex-1 | 17818 | 53677;53678;53679 | chr2:178565860;178565859;178565858 | chr2:179430587;179430586;179430585 |
| Novex-2 | 17885 | 53878;53879;53880 | chr2:178565860;178565859;178565858 | chr2:179430587;179430586;179430585 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs1705634558  |
None | 0.309 | N | 0.699 | 0.18 | 0.359557344763 | gnomAD-4.0.0 | 1.59159E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85919E-06 | 0 | 0 |
| M/R | None | None | 0.939 | N | 0.681 | 0.531 | 0.524946584802 | gnomAD-4.0.0 | 1.59158E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43279E-05 | 0 |
| M/T | None | None | 0.684 | N | 0.672 | 0.413 | 0.668175505125 | gnomAD-4.0.0 | 7.95788E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77331E-05 | None | 0 | 0 | 1.14365E-05 | 0 | 0 |
| M/V | None | None | 0.309 | N | 0.547 | 0.203 | 0.359963025489 | gnomAD-4.0.0 | 3.42133E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49779E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.4353 | ambiguous | 0.4745 | ambiguous | -2.447 | Highly Destabilizing | 0.004 | N | 0.4 | neutral | None | None | None | None | N |
| M/C | 0.6375 | likely_pathogenic | 0.6721 | pathogenic | -2.3 | Highly Destabilizing | 0.953 | D | 0.69 | prob.neutral | None | None | None | None | N |
| M/D | 0.9603 | likely_pathogenic | 0.9707 | pathogenic | -2.306 | Highly Destabilizing | 0.953 | D | 0.681 | prob.neutral | None | None | None | None | N |
| M/E | 0.7413 | likely_pathogenic | 0.7928 | pathogenic | -2.156 | Highly Destabilizing | 0.742 | D | 0.653 | neutral | None | None | None | None | N |
| M/F | 0.453 | ambiguous | 0.4849 | ambiguous | -0.992 | Destabilizing | 0.742 | D | 0.693 | prob.neutral | None | None | None | None | N |
| M/G | 0.7137 | likely_pathogenic | 0.7409 | pathogenic | -2.836 | Highly Destabilizing | 0.59 | D | 0.668 | neutral | None | None | None | None | N |
| M/H | 0.6884 | likely_pathogenic | 0.7533 | pathogenic | -2.246 | Highly Destabilizing | 0.996 | D | 0.677 | prob.neutral | None | None | None | None | N |
| M/I | 0.628 | likely_pathogenic | 0.6719 | pathogenic | -1.351 | Destabilizing | 0.309 | N | 0.699 | prob.neutral | N | 0.464703032 | None | None | N |
| M/K | 0.3903 | ambiguous | 0.4647 | ambiguous | -1.68 | Destabilizing | 0.684 | D | 0.66 | neutral | N | 0.472109007 | None | None | N |
| M/L | 0.1826 | likely_benign | 0.2091 | benign | -1.351 | Destabilizing | 0.001 | N | 0.26 | neutral | N | 0.40904175 | None | None | N |
| M/N | 0.7104 | likely_pathogenic | 0.7594 | pathogenic | -1.808 | Destabilizing | 0.953 | D | 0.659 | neutral | None | None | None | None | N |
| M/P | 0.9954 | likely_pathogenic | 0.9971 | pathogenic | -1.699 | Destabilizing | 0.953 | D | 0.651 | neutral | None | None | None | None | N |
| M/Q | 0.3468 | ambiguous | 0.3977 | ambiguous | -1.689 | Destabilizing | 0.953 | D | 0.699 | prob.neutral | None | None | None | None | N |
| M/R | 0.3814 | ambiguous | 0.4395 | ambiguous | -1.463 | Destabilizing | 0.939 | D | 0.681 | prob.neutral | N | 0.427491438 | None | None | N |
| M/S | 0.3764 | ambiguous | 0.4006 | ambiguous | -2.359 | Highly Destabilizing | 0.59 | D | 0.679 | prob.neutral | None | None | None | None | N |
| M/T | 0.2145 | likely_benign | 0.2516 | benign | -2.111 | Highly Destabilizing | 0.684 | D | 0.672 | neutral | N | 0.45188845 | None | None | N |
| M/V | 0.2013 | likely_benign | 0.2311 | benign | -1.699 | Destabilizing | 0.309 | N | 0.547 | neutral | N | 0.474418593 | None | None | N |
| M/W | 0.8153 | likely_pathogenic | 0.8408 | pathogenic | -1.221 | Destabilizing | 0.996 | D | 0.683 | prob.neutral | None | None | None | None | N |
| M/Y | 0.7481 | likely_pathogenic | 0.7729 | pathogenic | -1.258 | Destabilizing | 0.984 | D | 0.689 | 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.