Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17801 | 53626;53627;53628 | chr2:178607201;178607200;178607199 | chr2:179471928;179471927;179471926 |
| N2AB | 16160 | 48703;48704;48705 | chr2:178607201;178607200;178607199 | chr2:179471928;179471927;179471926 |
| N2A | 15233 | 45922;45923;45924 | chr2:178607201;178607200;178607199 | chr2:179471928;179471927;179471926 |
| N2B | 8736 | 26431;26432;26433 | chr2:178607201;178607200;178607199 | chr2:179471928;179471927;179471926 |
| Novex-1 | 8861 | 26806;26807;26808 | chr2:178607201;178607200;178607199 | chr2:179471928;179471927;179471926 |
| Novex-2 | 8928 | 27007;27008;27009 | chr2:178607201;178607200;178607199 | chr2:179471928;179471927;179471926 |
| 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 | rs1322346815  |
-2.051 | 0.782 | N | 0.645 | 0.379 | 0.631150896671 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| I/L | None | None | 0.084 | N | 0.326 | 0.055 | 0.449764926163 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/T | rs370929667 |
-3.653 | 0.505 | N | 0.601 | 0.468 | None | 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/T | rs370929667 |
-3.653 | 0.505 | N | 0.601 | 0.468 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs370929667 |
-3.653 | 0.505 | N | 0.601 | 0.468 | None | gnomAD-4.0.0 | 1.48804E-05 | None | None | None | None | N | None | 0 | 0 | None | 3.38135E-05 | 0 | None | 0 | 0 | 1.86552E-05 | 0 | 1.6021E-05 |
| I/V | rs1322346815 |
-2.121 | None | N | 0.211 | 0.05 | 0.313210971179 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-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 | 0.9235 | likely_pathogenic | 0.8941 | pathogenic | -3.045 | Highly Destabilizing | 0.218 | N | 0.637 | neutral | None | None | None | None | N |
| I/C | 0.9731 | likely_pathogenic | 0.964 | pathogenic | -2.122 | Highly Destabilizing | 0.973 | D | 0.791 | deleterious | None | None | None | None | N |
| I/D | 0.9996 | likely_pathogenic | 0.9995 | pathogenic | -3.777 | Highly Destabilizing | 0.967 | D | 0.858 | deleterious | None | None | None | None | N |
| I/E | 0.9978 | likely_pathogenic | 0.9974 | pathogenic | -3.468 | Highly Destabilizing | 0.906 | D | 0.834 | deleterious | None | None | None | None | N |
| I/F | 0.9405 | likely_pathogenic | 0.9231 | pathogenic | -1.85 | Destabilizing | 0.782 | D | 0.645 | neutral | N | 0.514896173 | None | None | N |
| I/G | 0.9959 | likely_pathogenic | 0.9949 | pathogenic | -3.636 | Highly Destabilizing | 0.906 | D | 0.805 | deleterious | None | None | None | None | N |
| I/H | 0.999 | likely_pathogenic | 0.9986 | pathogenic | -3.23 | Highly Destabilizing | 0.991 | D | 0.863 | deleterious | None | None | None | None | N |
| I/K | 0.9973 | likely_pathogenic | 0.9965 | pathogenic | -2.518 | Highly Destabilizing | 0.906 | D | 0.837 | deleterious | None | None | None | None | N |
| I/L | 0.462 | ambiguous | 0.4598 | ambiguous | -1.262 | Destabilizing | 0.084 | N | 0.326 | neutral | N | 0.471789294 | None | None | N |
| I/M | 0.6033 | likely_pathogenic | 0.5709 | pathogenic | -1.264 | Destabilizing | 0.782 | D | 0.635 | neutral | N | 0.491765488 | None | None | N |
| I/N | 0.9956 | likely_pathogenic | 0.9946 | pathogenic | -3.178 | Highly Destabilizing | 0.957 | D | 0.865 | deleterious | N | 0.515149662 | None | None | N |
| I/P | 0.9975 | likely_pathogenic | 0.9966 | pathogenic | -1.848 | Destabilizing | 0.967 | D | 0.86 | deleterious | None | None | None | None | N |
| I/Q | 0.9973 | likely_pathogenic | 0.9967 | pathogenic | -2.874 | Highly Destabilizing | 0.967 | D | 0.872 | deleterious | None | None | None | None | N |
| I/R | 0.9958 | likely_pathogenic | 0.9944 | pathogenic | -2.39 | Highly Destabilizing | 0.906 | D | 0.863 | deleterious | None | None | None | None | N |
| I/S | 0.9839 | likely_pathogenic | 0.9767 | pathogenic | -3.738 | Highly Destabilizing | 0.782 | D | 0.763 | deleterious | N | 0.515149662 | None | None | N |
| I/T | 0.8427 | likely_pathogenic | 0.7937 | pathogenic | -3.277 | Highly Destabilizing | 0.505 | D | 0.601 | neutral | N | 0.514896173 | None | None | N |
| I/V | 0.1097 | likely_benign | 0.0963 | benign | -1.848 | Destabilizing | None | N | 0.211 | neutral | N | 0.393453435 | None | None | N |
| I/W | 0.9988 | likely_pathogenic | 0.9983 | pathogenic | -2.306 | Highly Destabilizing | 0.991 | D | 0.845 | deleterious | None | None | None | None | N |
| I/Y | 0.9961 | likely_pathogenic | 0.9942 | pathogenic | -2.099 | Highly Destabilizing | 0.906 | D | 0.755 | 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.