Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16187 | 48784;48785;48786 | chr2:178615386;178615385;178615384 | chr2:179480113;179480112;179480111 |
| N2AB | 14546 | 43861;43862;43863 | chr2:178615386;178615385;178615384 | chr2:179480113;179480112;179480111 |
| N2A | 13619 | 41080;41081;41082 | chr2:178615386;178615385;178615384 | chr2:179480113;179480112;179480111 |
| N2B | 7122 | 21589;21590;21591 | chr2:178615386;178615385;178615384 | chr2:179480113;179480112;179480111 |
| Novex-1 | 7247 | 21964;21965;21966 | chr2:178615386;178615385;178615384 | chr2:179480113;179480112;179480111 |
| Novex-2 | 7314 | 22165;22166;22167 | chr2:178615386;178615385;178615384 | chr2:179480113;179480112;179480111 |
| 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/S | rs777279411  |
-2.146 | 0.998 | D | 0.816 | 0.527 | 0.889955871483 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| I/S | rs777279411 |
-2.146 | 0.998 | D | 0.816 | 0.527 | 0.889955871483 | gnomAD-4.0.0 | 5.47719E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.19972E-06 | 0 | 0 |
| I/V | rs1312494208 |
-1.424 | 0.333 | N | 0.264 | 0.087 | 0.472582640538 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/V | rs1312494208 |
-1.424 | 0.333 | N | 0.264 | 0.087 | 0.472582640538 | gnomAD-4.0.0 | 1.59365E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43377E-05 | 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 | 0.9824 | likely_pathogenic | 0.9664 | pathogenic | -2.273 | Highly Destabilizing | 0.992 | D | 0.667 | neutral | None | None | None | None | N |
| I/C | 0.9809 | likely_pathogenic | 0.9637 | pathogenic | -1.446 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| I/D | 0.9986 | likely_pathogenic | 0.9967 | pathogenic | -1.902 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| I/E | 0.9923 | likely_pathogenic | 0.9842 | pathogenic | -1.809 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| I/F | 0.9168 | likely_pathogenic | 0.8468 | pathogenic | -1.529 | Destabilizing | 0.998 | D | 0.752 | deleterious | D | 0.712392888 | None | None | N |
| I/G | 0.9951 | likely_pathogenic | 0.9887 | pathogenic | -2.704 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| I/H | 0.9961 | likely_pathogenic | 0.9902 | pathogenic | -1.919 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| I/K | 0.9852 | likely_pathogenic | 0.9664 | pathogenic | -1.568 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| I/L | 0.3687 | ambiguous | 0.2735 | benign | -1.097 | Destabilizing | 0.889 | D | 0.448 | neutral | D | 0.556213934 | None | None | N |
| I/M | 0.5912 | likely_pathogenic | 0.4528 | ambiguous | -0.844 | Destabilizing | 0.998 | D | 0.723 | prob.delet. | D | 0.732145945 | None | None | N |
| I/N | 0.9712 | likely_pathogenic | 0.9416 | pathogenic | -1.535 | Destabilizing | 0.999 | D | 0.843 | deleterious | D | 0.718643762 | None | None | N |
| I/P | 0.9525 | likely_pathogenic | 0.9207 | pathogenic | -1.463 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| I/Q | 0.9888 | likely_pathogenic | 0.9749 | pathogenic | -1.62 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| I/R | 0.9821 | likely_pathogenic | 0.9608 | pathogenic | -1.028 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| I/S | 0.9849 | likely_pathogenic | 0.968 | pathogenic | -2.258 | Highly Destabilizing | 0.998 | D | 0.816 | deleterious | D | 0.732808845 | None | None | N |
| I/T | 0.9715 | likely_pathogenic | 0.9453 | pathogenic | -2.036 | Highly Destabilizing | 0.989 | D | 0.789 | deleterious | D | 0.705358631 | None | None | N |
| I/V | 0.1687 | likely_benign | 0.1386 | benign | -1.463 | Destabilizing | 0.333 | N | 0.264 | neutral | N | 0.486197802 | None | None | N |
| I/W | 0.9972 | likely_pathogenic | 0.9931 | pathogenic | -1.706 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| I/Y | 0.9874 | likely_pathogenic | 0.9721 | pathogenic | -1.475 | Destabilizing | 1.0 | D | 0.791 | deleterious | 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.