Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21194 | 63805;63806;63807 | chr2:178587729;178587728;178587727 | chr2:179452456;179452455;179452454 |
| N2AB | 19553 | 58882;58883;58884 | chr2:178587729;178587728;178587727 | chr2:179452456;179452455;179452454 |
| N2A | 18626 | 56101;56102;56103 | chr2:178587729;178587728;178587727 | chr2:179452456;179452455;179452454 |
| N2B | 12129 | 36610;36611;36612 | chr2:178587729;178587728;178587727 | chr2:179452456;179452455;179452454 |
| Novex-1 | 12254 | 36985;36986;36987 | chr2:178587729;178587728;178587727 | chr2:179452456;179452455;179452454 |
| Novex-2 | 12321 | 37186;37187;37188 | chr2:178587729;178587728;178587727 | chr2:179452456;179452455;179452454 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | rs367838375  |
-1.82 | 1.0 | D | 0.865 | 0.829 | None | gnomAD-2.1.1 | 4.66E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.01998E-04 | 0 |
| L/P | rs367838375 |
-1.82 | 1.0 | D | 0.865 | 0.829 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.32411E-04 | 0 | 0 |
| L/P | rs367838375 |
-1.82 | 1.0 | D | 0.865 | 0.829 | None | gnomAD-4.0.0 | 1.61219E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.20464E-05 | 0 | 0 |
| L/V | None | None | 0.999 | D | 0.629 | 0.589 | 0.773388115084 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9668 | likely_pathogenic | 0.9612 | pathogenic | -1.611 | Destabilizing | 0.999 | D | 0.73 | prob.delet. | None | None | None | None | I |
| L/C | 0.9321 | likely_pathogenic | 0.9353 | pathogenic | -1.198 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | I |
| L/D | 0.9992 | likely_pathogenic | 0.9989 | pathogenic | -2.47 | Highly Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | I |
| L/E | 0.9965 | likely_pathogenic | 0.995 | pathogenic | -2.236 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | I |
| L/F | 0.7409 | likely_pathogenic | 0.7217 | pathogenic | -1.198 | Destabilizing | 1.0 | D | 0.763 | deleterious | N | 0.484744958 | None | None | I |
| L/G | 0.9937 | likely_pathogenic | 0.9919 | pathogenic | -2.018 | Highly Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | I |
| L/H | 0.9902 | likely_pathogenic | 0.9869 | pathogenic | -2.031 | Highly Destabilizing | 1.0 | D | 0.835 | deleterious | D | 0.642615251 | None | None | I |
| L/I | 0.1972 | likely_benign | 0.1988 | benign | -0.396 | Destabilizing | 0.999 | D | 0.611 | neutral | D | 0.562337974 | None | None | I |
| L/K | 0.9931 | likely_pathogenic | 0.9906 | pathogenic | -1.379 | Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | I |
| L/M | 0.3539 | ambiguous | 0.3653 | ambiguous | -0.672 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| L/N | 0.9944 | likely_pathogenic | 0.9933 | pathogenic | -1.98 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | I |
| L/P | 0.9922 | likely_pathogenic | 0.9899 | pathogenic | -0.793 | Destabilizing | 1.0 | D | 0.865 | deleterious | D | 0.642615251 | None | None | I |
| L/Q | 0.9866 | likely_pathogenic | 0.9811 | pathogenic | -1.641 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | I |
| L/R | 0.9883 | likely_pathogenic | 0.9829 | pathogenic | -1.7 | Destabilizing | 1.0 | D | 0.853 | deleterious | D | 0.642615251 | None | None | I |
| L/S | 0.995 | likely_pathogenic | 0.9936 | pathogenic | -2.294 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | I |
| L/T | 0.98 | likely_pathogenic | 0.9766 | pathogenic | -1.928 | Destabilizing | 1.0 | D | 0.822 | deleterious | None | None | None | None | I |
| L/V | 0.3358 | likely_benign | 0.3372 | benign | -0.793 | Destabilizing | 0.999 | D | 0.629 | neutral | D | 0.571028176 | None | None | I |
| L/W | 0.9799 | likely_pathogenic | 0.9748 | pathogenic | -1.512 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| L/Y | 0.9761 | likely_pathogenic | 0.9732 | pathogenic | -1.262 | Destabilizing | 1.0 | D | 0.794 | 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.