Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23467 | 70624;70625;70626 | chr2:178575733;178575732;178575731 | chr2:179440460;179440459;179440458 |
| N2AB | 21826 | 65701;65702;65703 | chr2:178575733;178575732;178575731 | chr2:179440460;179440459;179440458 |
| N2A | 20899 | 62920;62921;62922 | chr2:178575733;178575732;178575731 | chr2:179440460;179440459;179440458 |
| N2B | 14402 | 43429;43430;43431 | chr2:178575733;178575732;178575731 | chr2:179440460;179440459;179440458 |
| Novex-1 | 14527 | 43804;43805;43806 | chr2:178575733;178575732;178575731 | chr2:179440460;179440459;179440458 |
| Novex-2 | 14594 | 44005;44006;44007 | chr2:178575733;178575732;178575731 | chr2:179440460;179440459;179440458 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 0.95 | D | 0.706 | 0.408 | 0.618565862433 | gnomAD-4.0.0 | 1.59181E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.88253E-05 | 0 | 0 | 0 | 0 |
| I/T | rs778170654  |
-2.389 | 0.87 | N | 0.796 | 0.497 | 0.765417107005 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| I/V | rs866974760 |
None | 0.001 | N | 0.253 | 0.079 | 0.369682402691 | gnomAD-4.0.0 | 2.05293E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.47102E-04 | 0 | 0 | 1.65695E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9821 | likely_pathogenic | 0.9871 | pathogenic | -2.337 | Highly Destabilizing | 0.937 | D | 0.691 | prob.neutral | None | None | None | None | I |
| I/C | 0.98 | likely_pathogenic | 0.9839 | pathogenic | -1.561 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| I/D | 0.9991 | likely_pathogenic | 0.9993 | pathogenic | -2.043 | Highly Destabilizing | 0.998 | D | 0.829 | deleterious | None | None | None | None | I |
| I/E | 0.9968 | likely_pathogenic | 0.9974 | pathogenic | -1.972 | Destabilizing | 0.994 | D | 0.83 | deleterious | None | None | None | None | I |
| I/F | 0.9577 | likely_pathogenic | 0.9661 | pathogenic | -1.645 | Destabilizing | 0.976 | D | 0.745 | deleterious | None | None | None | None | I |
| I/G | 0.9968 | likely_pathogenic | 0.9978 | pathogenic | -2.755 | Highly Destabilizing | 0.995 | D | 0.823 | deleterious | None | None | None | None | I |
| I/H | 0.9978 | likely_pathogenic | 0.9984 | pathogenic | -1.973 | Destabilizing | 0.999 | D | 0.795 | deleterious | None | None | None | None | I |
| I/K | 0.993 | likely_pathogenic | 0.9948 | pathogenic | -1.716 | Destabilizing | 0.823 | D | 0.83 | deleterious | D | 0.536479467 | None | None | I |
| I/L | 0.5219 | ambiguous | 0.5502 | ambiguous | -1.204 | Destabilizing | 0.056 | N | 0.478 | neutral | N | 0.495063036 | None | None | I |
| I/M | 0.6591 | likely_pathogenic | 0.6792 | pathogenic | -0.921 | Destabilizing | 0.95 | D | 0.706 | prob.neutral | D | 0.542213459 | None | None | I |
| I/N | 0.9768 | likely_pathogenic | 0.9805 | pathogenic | -1.633 | Destabilizing | 0.998 | D | 0.831 | deleterious | None | None | None | None | I |
| I/P | 0.9688 | likely_pathogenic | 0.9782 | pathogenic | -1.555 | Destabilizing | 0.998 | D | 0.834 | deleterious | None | None | None | None | I |
| I/Q | 0.9954 | likely_pathogenic | 0.9962 | pathogenic | -1.752 | Destabilizing | 0.996 | D | 0.829 | deleterious | None | None | None | None | I |
| I/R | 0.9926 | likely_pathogenic | 0.9947 | pathogenic | -1.113 | Destabilizing | 0.984 | D | 0.831 | deleterious | D | 0.554583722 | None | None | I |
| I/S | 0.9871 | likely_pathogenic | 0.99 | pathogenic | -2.322 | Highly Destabilizing | 0.995 | D | 0.794 | deleterious | None | None | None | None | I |
| I/T | 0.9694 | likely_pathogenic | 0.9745 | pathogenic | -2.121 | Highly Destabilizing | 0.87 | D | 0.796 | deleterious | N | 0.519589753 | None | None | I |
| I/V | 0.1068 | likely_benign | 0.1169 | benign | -1.555 | Destabilizing | 0.001 | N | 0.253 | neutral | N | 0.460841581 | None | None | I |
| I/W | 0.9991 | likely_pathogenic | 0.9993 | pathogenic | -1.792 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| I/Y | 0.9938 | likely_pathogenic | 0.995 | pathogenic | -1.588 | Destabilizing | 0.907 | D | 0.771 | deleterious | None | None | None | None | I |
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.