Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21486 | 64681;64682;64683 | chr2:178585288;178585287;178585286 | chr2:179450015;179450014;179450013 |
| N2AB | 19845 | 59758;59759;59760 | chr2:178585288;178585287;178585286 | chr2:179450015;179450014;179450013 |
| N2A | 18918 | 56977;56978;56979 | chr2:178585288;178585287;178585286 | chr2:179450015;179450014;179450013 |
| N2B | 12421 | 37486;37487;37488 | chr2:178585288;178585287;178585286 | chr2:179450015;179450014;179450013 |
| Novex-1 | 12546 | 37861;37862;37863 | chr2:178585288;178585287;178585286 | chr2:179450015;179450014;179450013 |
| Novex-2 | 12613 | 38062;38063;38064 | chr2:178585288;178585287;178585286 | chr2:179450015;179450014;179450013 |
| 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/F | rs779988742  |
-1.39 | 0.317 | N | 0.653 | 0.18 | 0.245660935333 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| I/F | rs779988742 |
-1.39 | 0.317 | N | 0.653 | 0.18 | 0.245660935333 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/F | rs779988742 |
-1.39 | 0.317 | N | 0.653 | 0.18 | 0.245660935333 | gnomAD-4.0.0 | 4.96352E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.9376E-06 | 0 | 1.60287E-05 |
| I/N | None | None | None | N | 0.592 | 0.413 | 0.670625927506 | gnomAD-4.0.0 | 4.79534E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.30092E-06 | 0 | 0 |
| I/T | None | None | 0.062 | N | 0.675 | 0.395 | 0.541330971987 | gnomAD-4.0.0 | 6.85048E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00132E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5957 | likely_pathogenic | 0.5449 | ambiguous | -2.667 | Highly Destabilizing | 0.035 | N | 0.66 | neutral | None | None | None | None | I |
| I/C | 0.8706 | likely_pathogenic | 0.8628 | pathogenic | -2.005 | Highly Destabilizing | 0.824 | D | 0.741 | deleterious | None | None | None | None | I |
| I/D | 0.9966 | likely_pathogenic | 0.9937 | pathogenic | -3.421 | Highly Destabilizing | 0.235 | N | 0.789 | deleterious | None | None | None | None | I |
| I/E | 0.9873 | likely_pathogenic | 0.9791 | pathogenic | -3.15 | Highly Destabilizing | 0.149 | N | 0.793 | deleterious | None | None | None | None | I |
| I/F | 0.4341 | ambiguous | 0.3542 | ambiguous | -1.777 | Destabilizing | 0.317 | N | 0.653 | neutral | N | 0.443677186 | None | None | I |
| I/G | 0.9573 | likely_pathogenic | 0.9316 | pathogenic | -3.179 | Highly Destabilizing | 0.081 | N | 0.78 | deleterious | None | None | None | None | I |
| I/H | 0.9879 | likely_pathogenic | 0.9804 | pathogenic | -2.647 | Highly Destabilizing | 0.698 | D | 0.813 | deleterious | None | None | None | None | I |
| I/K | 0.9838 | likely_pathogenic | 0.974 | pathogenic | -2.309 | Highly Destabilizing | 0.235 | N | 0.793 | deleterious | None | None | None | None | I |
| I/L | 0.1476 | likely_benign | 0.1352 | benign | -1.139 | Destabilizing | 0.012 | N | 0.452 | neutral | N | 0.382396654 | None | None | I |
| I/M | 0.1704 | likely_benign | 0.1546 | benign | -1.135 | Destabilizing | 0.317 | N | 0.636 | neutral | N | 0.493501078 | None | None | I |
| I/N | 0.9723 | likely_pathogenic | 0.9548 | pathogenic | -2.895 | Highly Destabilizing | None | N | 0.592 | neutral | N | 0.503609682 | None | None | I |
| I/P | 0.986 | likely_pathogenic | 0.9814 | pathogenic | -1.639 | Destabilizing | 0.555 | D | 0.815 | deleterious | None | None | None | None | I |
| I/Q | 0.9779 | likely_pathogenic | 0.9664 | pathogenic | -2.662 | Highly Destabilizing | 0.38 | N | 0.821 | deleterious | None | None | None | None | I |
| I/R | 0.9741 | likely_pathogenic | 0.9585 | pathogenic | -2.208 | Highly Destabilizing | 0.38 | N | 0.819 | deleterious | None | None | None | None | I |
| I/S | 0.9095 | likely_pathogenic | 0.8718 | pathogenic | -3.435 | Highly Destabilizing | 0.062 | N | 0.763 | deleterious | N | 0.503609682 | None | None | I |
| I/T | 0.6907 | likely_pathogenic | 0.6421 | pathogenic | -3.012 | Highly Destabilizing | 0.062 | N | 0.675 | prob.neutral | N | 0.503356192 | None | None | I |
| I/V | 0.0748 | likely_benign | 0.0737 | benign | -1.639 | Destabilizing | None | N | 0.219 | neutral | N | 0.439359949 | None | None | I |
| I/W | 0.9725 | likely_pathogenic | 0.9591 | pathogenic | -2.084 | Highly Destabilizing | 0.935 | D | 0.817 | deleterious | None | None | None | None | I |
| I/Y | 0.9303 | likely_pathogenic | 0.891 | pathogenic | -1.849 | Destabilizing | 0.555 | D | 0.755 | 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.