Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3116 | 9571;9572;9573 | chr2:178767884;178767883;178767882 | chr2:179632611;179632610;179632609 |
| N2AB | 3116 | 9571;9572;9573 | chr2:178767884;178767883;178767882 | chr2:179632611;179632610;179632609 |
| N2A | 3116 | 9571;9572;9573 | chr2:178767884;178767883;178767882 | chr2:179632611;179632610;179632609 |
| N2B | 3070 | 9433;9434;9435 | chr2:178767884;178767883;178767882 | chr2:179632611;179632610;179632609 |
| Novex-1 | 3070 | 9433;9434;9435 | chr2:178767884;178767883;178767882 | chr2:179632611;179632610;179632609 |
| Novex-2 | 3070 | 9433;9434;9435 | chr2:178767884;178767883;178767882 | chr2:179632611;179632610;179632609 |
| Novex-3 | 3116 | 9571;9572;9573 | chr2:178767884;178767883;178767882 | chr2:179632611;179632610;179632609 |
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 | rs760230943  |
-1.193 | 1.0 | D | 0.761 | 0.638 | 0.674575032278 | gnomAD-2.1.1 | 5.58E-05 | None | None | None | None | N | None | 0 | 4.05069E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/M | rs760230943 |
-1.193 | 1.0 | D | 0.761 | 0.638 | 0.674575032278 | gnomAD-4.0.0 | 2.06774E-05 | None | None | None | None | N | None | 0 | 2.97252E-04 | 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 | 0.9838 | likely_pathogenic | 0.9911 | pathogenic | -2.961 | Highly Destabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | N |
| I/C | 0.9833 | likely_pathogenic | 0.9907 | pathogenic | -2.348 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| I/D | 0.9984 | likely_pathogenic | 0.9992 | pathogenic | -3.282 | Highly Destabilizing | 1.0 | D | 0.846 | deleterious | None | None | None | None | N |
| I/E | 0.996 | likely_pathogenic | 0.9977 | pathogenic | -3.053 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| I/F | 0.2921 | likely_benign | 0.4189 | ambiguous | -1.794 | Destabilizing | 1.0 | D | 0.816 | deleterious | D | 0.658641645 | None | None | N |
| I/G | 0.9974 | likely_pathogenic | 0.9986 | pathogenic | -3.522 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| I/H | 0.9728 | likely_pathogenic | 0.9873 | pathogenic | -2.872 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| I/K | 0.9868 | likely_pathogenic | 0.993 | pathogenic | -2.491 | Highly Destabilizing | 1.0 | D | 0.846 | deleterious | None | None | None | None | N |
| I/L | 0.2013 | likely_benign | 0.2546 | benign | -1.328 | Destabilizing | 0.993 | D | 0.431 | neutral | D | 0.547606198 | None | None | N |
| I/M | 0.3079 | likely_benign | 0.4052 | ambiguous | -1.289 | Destabilizing | 1.0 | D | 0.761 | deleterious | D | 0.752656777 | None | None | N |
| I/N | 0.9691 | likely_pathogenic | 0.984 | pathogenic | -2.841 | Highly Destabilizing | 1.0 | D | 0.865 | deleterious | D | 0.806127867 | None | None | N |
| I/P | 0.9979 | likely_pathogenic | 0.9984 | pathogenic | -1.855 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| I/Q | 0.9822 | likely_pathogenic | 0.9909 | pathogenic | -2.705 | Highly Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | N |
| I/R | 0.9785 | likely_pathogenic | 0.9883 | pathogenic | -2.092 | Highly Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| I/S | 0.9751 | likely_pathogenic | 0.9871 | pathogenic | -3.564 | Highly Destabilizing | 1.0 | D | 0.846 | deleterious | D | 0.806127867 | None | None | N |
| I/T | 0.9853 | likely_pathogenic | 0.9924 | pathogenic | -3.188 | Highly Destabilizing | 1.0 | D | 0.81 | deleterious | D | 0.750513603 | None | None | N |
| I/V | 0.3319 | likely_benign | 0.4226 | ambiguous | -1.855 | Destabilizing | 0.993 | D | 0.411 | neutral | D | 0.629914955 | None | None | N |
| I/W | 0.9668 | likely_pathogenic | 0.9829 | pathogenic | -2.167 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| I/Y | 0.8677 | likely_pathogenic | 0.9272 | pathogenic | -1.945 | Destabilizing | 1.0 | D | 0.817 | 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.