Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16588 | 49987;49988;49989 | chr2:178612959;178612958;178612957 | chr2:179477686;179477685;179477684 |
| N2AB | 14947 | 45064;45065;45066 | chr2:178612959;178612958;178612957 | chr2:179477686;179477685;179477684 |
| N2A | 14020 | 42283;42284;42285 | chr2:178612959;178612958;178612957 | chr2:179477686;179477685;179477684 |
| N2B | 7523 | 22792;22793;22794 | chr2:178612959;178612958;178612957 | chr2:179477686;179477685;179477684 |
| Novex-1 | 7648 | 23167;23168;23169 | chr2:178612959;178612958;178612957 | chr2:179477686;179477685;179477684 |
| Novex-2 | 7715 | 23368;23369;23370 | chr2:178612959;178612958;178612957 | chr2:179477686;179477685;179477684 |
| 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/T | rs1352705790  |
-3.697 | 0.978 | D | 0.68 | 0.566 | 0.852183005683 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| I/T | rs1352705790 |
-3.697 | 0.978 | D | 0.68 | 0.566 | 0.852183005683 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs1352705790 |
-3.697 | 0.978 | D | 0.68 | 0.566 | 0.852183005683 | gnomAD-4.0.0 | 2.48049E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39196E-06 | 0 | 0 |
| I/V | rs1251831852 |
None | 0.198 | N | 0.197 | 0.121 | 0.392855499163 | gnomAD-4.0.0 | 2.73852E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73732E-04 | 2.69946E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.924 | likely_pathogenic | 0.9283 | pathogenic | -3.213 | Highly Destabilizing | 0.983 | D | 0.682 | prob.neutral | None | None | None | None | N |
| I/C | 0.9827 | likely_pathogenic | 0.9803 | pathogenic | -2.542 | Highly Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| I/D | 0.9995 | likely_pathogenic | 0.9997 | pathogenic | -4.058 | Highly Destabilizing | 0.999 | D | 0.899 | deleterious | None | None | None | None | N |
| I/E | 0.9979 | likely_pathogenic | 0.9986 | pathogenic | -3.743 | Highly Destabilizing | 0.999 | D | 0.896 | deleterious | None | None | None | None | N |
| I/F | 0.8239 | likely_pathogenic | 0.8334 | pathogenic | -1.964 | Destabilizing | 0.997 | D | 0.647 | neutral | D | 0.690202871 | None | None | N |
| I/G | 0.9964 | likely_pathogenic | 0.997 | pathogenic | -3.797 | Highly Destabilizing | 0.999 | D | 0.892 | deleterious | None | None | None | None | N |
| I/H | 0.9985 | likely_pathogenic | 0.999 | pathogenic | -3.365 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| I/K | 0.9965 | likely_pathogenic | 0.9977 | pathogenic | -2.783 | Highly Destabilizing | 0.999 | D | 0.898 | deleterious | None | None | None | None | N |
| I/L | 0.384 | ambiguous | 0.3462 | ambiguous | -1.435 | Destabilizing | 0.798 | D | 0.33 | neutral | N | 0.483840966 | None | None | N |
| I/M | 0.4265 | ambiguous | 0.4366 | ambiguous | -1.602 | Destabilizing | 0.997 | D | 0.643 | neutral | D | 0.578961995 | None | None | N |
| I/N | 0.995 | likely_pathogenic | 0.9967 | pathogenic | -3.51 | Highly Destabilizing | 0.999 | D | 0.913 | deleterious | D | 0.691440194 | None | None | N |
| I/P | 0.9968 | likely_pathogenic | 0.9975 | pathogenic | -2.022 | Highly Destabilizing | 0.999 | D | 0.903 | deleterious | None | None | None | None | N |
| I/Q | 0.9969 | likely_pathogenic | 0.9979 | pathogenic | -3.189 | Highly Destabilizing | 0.999 | D | 0.915 | deleterious | None | None | None | None | N |
| I/R | 0.9945 | likely_pathogenic | 0.9964 | pathogenic | -2.665 | Highly Destabilizing | 0.999 | D | 0.915 | deleterious | None | None | None | None | N |
| I/S | 0.9816 | likely_pathogenic | 0.9867 | pathogenic | -4.034 | Highly Destabilizing | 0.997 | D | 0.827 | deleterious | D | 0.691440194 | None | None | N |
| I/T | 0.8555 | likely_pathogenic | 0.8808 | pathogenic | -3.566 | Highly Destabilizing | 0.978 | D | 0.68 | prob.neutral | D | 0.690202871 | None | None | N |
| I/V | 0.1244 | likely_benign | 0.1111 | benign | -2.022 | Highly Destabilizing | 0.198 | N | 0.197 | neutral | N | 0.397057948 | None | None | N |
| I/W | 0.9965 | likely_pathogenic | 0.9973 | pathogenic | -2.365 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| I/Y | 0.9915 | likely_pathogenic | 0.993 | pathogenic | -2.234 | Highly Destabilizing | 0.999 | D | 0.761 | 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.