Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25923 | 77992;77993;77994 | chr2:178568365;178568364;178568363 | chr2:179433092;179433091;179433090 |
| N2AB | 24282 | 73069;73070;73071 | chr2:178568365;178568364;178568363 | chr2:179433092;179433091;179433090 |
| N2A | 23355 | 70288;70289;70290 | chr2:178568365;178568364;178568363 | chr2:179433092;179433091;179433090 |
| N2B | 16858 | 50797;50798;50799 | chr2:178568365;178568364;178568363 | chr2:179433092;179433091;179433090 |
| Novex-1 | 16983 | 51172;51173;51174 | chr2:178568365;178568364;178568363 | chr2:179433092;179433091;179433090 |
| Novex-2 | 17050 | 51373;51374;51375 | chr2:178568365;178568364;178568363 | chr2:179433092;179433091;179433090 |
| 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/M | rs780766847  |
-1.016 | 1.0 | N | 0.831 | 0.43 | 0.479133204078 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/M | rs780766847 |
-1.016 | 1.0 | N | 0.831 | 0.43 | 0.479133204078 | gnomAD-4.0.0 | 6.84418E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.1595E-05 | 0 |
| I/T | rs1706767916 |
None | 1.0 | D | 0.854 | 0.585 | 0.758052853744 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1706767916 |
None | 1.0 | D | 0.854 | 0.585 | 0.758052853744 | gnomAD-4.0.0 | 6.5741E-06 | None | None | None | None | I | None | 2.41266E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.9797 | likely_pathogenic | 0.9868 | pathogenic | -2.37 | Highly Destabilizing | 0.999 | D | 0.678 | prob.neutral | None | None | None | None | I |
| I/C | 0.9877 | likely_pathogenic | 0.9898 | pathogenic | -1.401 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | I |
| I/D | 0.999 | likely_pathogenic | 0.9992 | pathogenic | -2.236 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | I |
| I/E | 0.9964 | likely_pathogenic | 0.9974 | pathogenic | -2.185 | Highly Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | I |
| I/F | 0.9418 | likely_pathogenic | 0.9594 | pathogenic | -1.746 | Destabilizing | 1.0 | D | 0.85 | deleterious | D | 0.536716049 | None | None | I |
| I/G | 0.9969 | likely_pathogenic | 0.9977 | pathogenic | -2.767 | Highly Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | None | None | I |
| I/H | 0.9977 | likely_pathogenic | 0.9983 | pathogenic | -2.016 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | I |
| I/K | 0.9926 | likely_pathogenic | 0.9943 | pathogenic | -1.721 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | I |
| I/L | 0.522 | ambiguous | 0.5413 | ambiguous | -1.296 | Destabilizing | 0.993 | D | 0.431 | neutral | N | 0.474490019 | None | None | I |
| I/M | 0.5648 | likely_pathogenic | 0.6354 | pathogenic | -0.86 | Destabilizing | 1.0 | D | 0.831 | deleterious | N | 0.521146689 | None | None | I |
| I/N | 0.9744 | likely_pathogenic | 0.98 | pathogenic | -1.598 | Destabilizing | 1.0 | D | 0.881 | deleterious | D | 0.533516953 | None | None | I |
| I/P | 0.9621 | likely_pathogenic | 0.9745 | pathogenic | -1.628 | Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | None | I |
| I/Q | 0.9947 | likely_pathogenic | 0.9962 | pathogenic | -1.753 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | I |
| I/R | 0.9927 | likely_pathogenic | 0.9939 | pathogenic | -1.07 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | I |
| I/S | 0.9875 | likely_pathogenic | 0.9908 | pathogenic | -2.224 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | D | 0.539504434 | None | None | I |
| I/T | 0.9655 | likely_pathogenic | 0.9783 | pathogenic | -2.053 | Highly Destabilizing | 1.0 | D | 0.854 | deleterious | D | 0.532756484 | None | None | I |
| I/V | 0.1422 | likely_benign | 0.1723 | benign | -1.628 | Destabilizing | 0.993 | D | 0.405 | neutral | N | 0.483198366 | None | None | I |
| I/W | 0.9989 | likely_pathogenic | 0.9991 | pathogenic | -1.913 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | I |
| I/Y | 0.9931 | likely_pathogenic | 0.9941 | pathogenic | -1.719 | Destabilizing | 1.0 | D | 0.867 | 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.