Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1859 | 5800;5801;5802 | chr2:178776289;178776288;178776287 | chr2:179641016;179641015;179641014 |
| N2AB | 1859 | 5800;5801;5802 | chr2:178776289;178776288;178776287 | chr2:179641016;179641015;179641014 |
| N2A | 1859 | 5800;5801;5802 | chr2:178776289;178776288;178776287 | chr2:179641016;179641015;179641014 |
| N2B | 1813 | 5662;5663;5664 | chr2:178776289;178776288;178776287 | chr2:179641016;179641015;179641014 |
| Novex-1 | 1813 | 5662;5663;5664 | chr2:178776289;178776288;178776287 | chr2:179641016;179641015;179641014 |
| Novex-2 | 1813 | 5662;5663;5664 | chr2:178776289;178776288;178776287 | chr2:179641016;179641015;179641014 |
| Novex-3 | 1859 | 5800;5801;5802 | chr2:178776289;178776288;178776287 | chr2:179641016;179641015;179641014 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/M | rs777923620  |
-0.536 | 1.0 | D | 0.677 | 0.507 | 0.476522311808 | gnomAD-2.1.1 | 7.96E-06 | None | None | None | None | N | None | 0 | 5.78E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/M | rs777923620 |
-0.536 | 1.0 | D | 0.677 | 0.507 | 0.476522311808 | gnomAD-4.0.0 | 1.59062E-06 | None | None | None | None | N | None | 0 | 2.28634E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs551538420 |
-0.943 | 0.978 | N | 0.644 | 0.424 | 0.346315397577 | gnomAD-2.1.1 | 5.31E-05 | None | None | None | None | N | None | 8.01E-05 | 0 | None | 9.65E-05 | 2.00562E-04 | None | 0 | None | 7.98E-05 | 4.65E-05 | 0 |
| R/S | rs551538420 |
-0.943 | 0.978 | N | 0.644 | 0.424 | 0.346315397577 | gnomAD-3.1.2 | 7.89E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 3.84911E-04 | None | 0 | 0 | 8.82E-05 | 0 | 0 |
| R/S | rs551538420 |
-0.943 | 0.978 | N | 0.644 | 0.424 | 0.346315397577 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/S | rs551538420 |
-0.943 | 0.978 | N | 0.644 | 0.424 | 0.346315397577 | gnomAD-4.0.0 | 1.31342E-04 | None | None | None | None | N | None | 7.99637E-05 | 0 | None | 3.37792E-05 | 1.11403E-04 | None | 9.37471E-05 | 0 | 1.61865E-04 | 1.09791E-05 | 3.1998E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.902 | likely_pathogenic | 0.8732 | pathogenic | -0.919 | Destabilizing | 0.983 | D | 0.615 | neutral | None | None | None | None | N |
| R/C | 0.6156 | likely_pathogenic | 0.5476 | ambiguous | -0.816 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| R/D | 0.9835 | likely_pathogenic | 0.9783 | pathogenic | -0.123 | Destabilizing | 0.998 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/E | 0.9075 | likely_pathogenic | 0.8787 | pathogenic | 0.04 | Stabilizing | 0.983 | D | 0.609 | neutral | None | None | None | None | N |
| R/F | 0.9446 | likely_pathogenic | 0.9288 | pathogenic | -0.612 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | None | None | None | None | N |
| R/G | 0.8751 | likely_pathogenic | 0.8361 | pathogenic | -1.255 | Destabilizing | 0.989 | D | 0.64 | neutral | D | 0.680747921 | None | None | N |
| R/H | 0.2845 | likely_benign | 0.2397 | benign | -1.677 | Destabilizing | 0.999 | D | 0.679 | prob.neutral | None | None | None | None | N |
| R/I | 0.7977 | likely_pathogenic | 0.7526 | pathogenic | -0.002 | Destabilizing | 0.999 | D | 0.718 | prob.delet. | None | None | None | None | N |
| R/K | 0.2645 | likely_benign | 0.2451 | benign | -0.715 | Destabilizing | 0.37 | N | 0.346 | neutral | N | 0.475629951 | None | None | N |
| R/L | 0.7695 | likely_pathogenic | 0.7203 | pathogenic | -0.002 | Destabilizing | 0.992 | D | 0.64 | neutral | None | None | None | None | N |
| R/M | 0.8662 | likely_pathogenic | 0.8319 | pathogenic | -0.442 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | D | 0.541566096 | None | None | N |
| R/N | 0.9513 | likely_pathogenic | 0.9363 | pathogenic | -0.404 | Destabilizing | 0.998 | D | 0.672 | neutral | None | None | None | None | N |
| R/P | 0.9891 | likely_pathogenic | 0.9864 | pathogenic | -0.288 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/Q | 0.355 | ambiguous | 0.2958 | benign | -0.441 | Destabilizing | 0.995 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/S | 0.9081 | likely_pathogenic | 0.8781 | pathogenic | -1.148 | Destabilizing | 0.978 | D | 0.644 | neutral | N | 0.493088865 | None | None | N |
| R/T | 0.7928 | likely_pathogenic | 0.7385 | pathogenic | -0.777 | Destabilizing | 0.997 | D | 0.691 | prob.neutral | N | 0.49424768 | None | None | N |
| R/V | 0.8029 | likely_pathogenic | 0.76 | pathogenic | -0.288 | Destabilizing | 0.998 | D | 0.716 | prob.delet. | None | None | None | None | N |
| R/W | 0.7425 | likely_pathogenic | 0.6841 | pathogenic | -0.286 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | D | 0.643856327 | None | None | N |
| R/Y | 0.8787 | likely_pathogenic | 0.8433 | pathogenic | -0.031 | Destabilizing | 0.999 | D | 0.705 | prob.neutral | 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.