Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20871 | 62836;62837;62838 | chr2:178589114;178589113;178589112 | chr2:179453841;179453840;179453839 |
| N2AB | 19230 | 57913;57914;57915 | chr2:178589114;178589113;178589112 | chr2:179453841;179453840;179453839 |
| N2A | 18303 | 55132;55133;55134 | chr2:178589114;178589113;178589112 | chr2:179453841;179453840;179453839 |
| N2B | 11806 | 35641;35642;35643 | chr2:178589114;178589113;178589112 | chr2:179453841;179453840;179453839 |
| Novex-1 | 11931 | 36016;36017;36018 | chr2:178589114;178589113;178589112 | chr2:179453841;179453840;179453839 |
| Novex-2 | 11998 | 36217;36218;36219 | chr2:178589114;178589113;178589112 | chr2:179453841;179453840;179453839 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/M | rs767670018  |
None | 0.76 | N | 0.65 | 0.284 | 0.632073011451 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/M | rs767670018 |
None | 0.76 | N | 0.65 | 0.284 | 0.632073011451 | gnomAD-4.0.0 | 2.48181E-06 | None | None | None | None | N | None | 4.00534E-05 | 0 | None | 0 | 0 | None | 1.6001E-05 | 0 | 0 | 0 | 0 |
| L/V | rs767670018 |
-1.444 | 0.76 | N | 0.739 | 0.181 | None | gnomAD-2.1.1 | 3.24E-05 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.24E-05 | 0 |
| L/V | rs767670018 |
-1.444 | 0.76 | N | 0.739 | 0.181 | None | 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 |
| L/V | rs767670018 |
-1.444 | 0.76 | N | 0.739 | 0.181 | None | gnomAD-4.0.0 | 6.63884E-05 | None | None | None | None | N | None | 1.33511E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.81649E-05 | 0 | 3.20338E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.8938 | likely_pathogenic | 0.8717 | pathogenic | -2.442 | Highly Destabilizing | 0.953 | D | 0.727 | prob.delet. | None | None | None | None | N |
| L/C | 0.8261 | likely_pathogenic | 0.8132 | pathogenic | -1.727 | Destabilizing | 0.999 | D | 0.766 | deleterious | None | None | None | None | N |
| L/D | 0.9984 | likely_pathogenic | 0.9976 | pathogenic | -2.808 | Highly Destabilizing | 0.998 | D | 0.865 | deleterious | None | None | None | None | N |
| L/E | 0.9914 | likely_pathogenic | 0.9869 | pathogenic | -2.662 | Highly Destabilizing | 0.998 | D | 0.86 | deleterious | None | None | None | None | N |
| L/F | 0.5841 | likely_pathogenic | 0.436 | ambiguous | -1.549 | Destabilizing | 0.986 | D | 0.828 | deleterious | None | None | None | None | N |
| L/G | 0.9804 | likely_pathogenic | 0.9732 | pathogenic | -2.922 | Highly Destabilizing | 0.993 | D | 0.853 | deleterious | None | None | None | None | N |
| L/H | 0.9799 | likely_pathogenic | 0.9707 | pathogenic | -2.403 | Highly Destabilizing | 0.999 | D | 0.85 | deleterious | None | None | None | None | N |
| L/I | 0.1342 | likely_benign | 0.1107 | benign | -1.088 | Destabilizing | 0.128 | N | 0.448 | neutral | None | None | None | None | N |
| L/K | 0.9834 | likely_pathogenic | 0.9795 | pathogenic | -1.891 | Destabilizing | 0.993 | D | 0.834 | deleterious | None | None | None | None | N |
| L/M | 0.2303 | likely_benign | 0.1948 | benign | -0.946 | Destabilizing | 0.76 | D | 0.65 | neutral | N | 0.487855149 | None | None | N |
| L/N | 0.9865 | likely_pathogenic | 0.983 | pathogenic | -2.031 | Highly Destabilizing | 0.998 | D | 0.865 | deleterious | None | None | None | None | N |
| L/P | 0.8577 | likely_pathogenic | 0.8331 | pathogenic | -1.517 | Destabilizing | 0.997 | D | 0.866 | deleterious | N | 0.495671805 | None | None | N |
| L/Q | 0.9602 | likely_pathogenic | 0.9437 | pathogenic | -2.021 | Highly Destabilizing | 0.991 | D | 0.855 | deleterious | D | 0.529685973 | None | None | N |
| L/R | 0.9733 | likely_pathogenic | 0.9656 | pathogenic | -1.471 | Destabilizing | 0.991 | D | 0.846 | deleterious | D | 0.529685973 | None | None | N |
| L/S | 0.9811 | likely_pathogenic | 0.9722 | pathogenic | -2.661 | Highly Destabilizing | 0.993 | D | 0.837 | deleterious | None | None | None | None | N |
| L/T | 0.8539 | likely_pathogenic | 0.8241 | pathogenic | -2.387 | Highly Destabilizing | 0.986 | D | 0.804 | deleterious | None | None | None | None | N |
| L/V | 0.145 | likely_benign | 0.1213 | benign | -1.517 | Destabilizing | 0.76 | D | 0.739 | prob.delet. | N | 0.467980985 | None | None | N |
| L/W | 0.936 | likely_pathogenic | 0.8838 | pathogenic | -1.928 | Destabilizing | 0.999 | D | 0.811 | deleterious | None | None | None | None | N |
| L/Y | 0.9637 | likely_pathogenic | 0.9375 | pathogenic | -1.66 | Destabilizing | 0.998 | D | 0.809 | 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.