Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22647 | 68164;68165;68166 | chr2:178579091;178579090;178579089 | chr2:179443818;179443817;179443816 |
| N2AB | 21006 | 63241;63242;63243 | chr2:178579091;178579090;178579089 | chr2:179443818;179443817;179443816 |
| N2A | 20079 | 60460;60461;60462 | chr2:178579091;178579090;178579089 | chr2:179443818;179443817;179443816 |
| N2B | 13582 | 40969;40970;40971 | chr2:178579091;178579090;178579089 | chr2:179443818;179443817;179443816 |
| Novex-1 | 13707 | 41344;41345;41346 | chr2:178579091;178579090;178579089 | chr2:179443818;179443817;179443816 |
| Novex-2 | 13774 | 41545;41546;41547 | chr2:178579091;178579090;178579089 | chr2:179443818;179443817;179443816 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | None | None | 0.948 | D | 0.694 | 0.613 | 0.495438931914 | gnomAD-4.0.0 | 1.36876E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31889E-05 | 0 |
| P/L | None | None | 0.978 | D | 0.783 | 0.64 | 0.757105107938 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| P/S | rs1451467519  |
-2.771 | 0.989 | D | 0.738 | 0.668 | 0.576573652137 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/S | rs1451467519 |
-2.771 | 0.989 | D | 0.738 | 0.668 | 0.576573652137 | gnomAD-4.0.0 | 1.50564E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79925E-05 | 2.31889E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.7694 | likely_pathogenic | 0.7067 | pathogenic | -2.309 | Highly Destabilizing | 0.948 | D | 0.694 | prob.neutral | D | 0.549615436 | None | None | N |
| P/C | 0.9391 | likely_pathogenic | 0.9244 | pathogenic | -2.142 | Highly Destabilizing | 0.154 | N | 0.628 | neutral | None | None | None | None | N |
| P/D | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -3.214 | Highly Destabilizing | 0.999 | D | 0.756 | deleterious | None | None | None | None | N |
| P/E | 0.9979 | likely_pathogenic | 0.9983 | pathogenic | -2.99 | Highly Destabilizing | 0.999 | D | 0.753 | deleterious | None | None | None | None | N |
| P/F | 0.9984 | likely_pathogenic | 0.9983 | pathogenic | -1.35 | Destabilizing | 0.999 | D | 0.857 | deleterious | None | None | None | None | N |
| P/G | 0.9917 | likely_pathogenic | 0.9916 | pathogenic | -2.842 | Highly Destabilizing | 0.998 | D | 0.765 | deleterious | None | None | None | None | N |
| P/H | 0.9975 | likely_pathogenic | 0.9977 | pathogenic | -2.551 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | D | 0.605940365 | None | None | N |
| P/I | 0.8412 | likely_pathogenic | 0.8362 | pathogenic | -0.807 | Destabilizing | 0.998 | D | 0.851 | deleterious | None | None | None | None | N |
| P/K | 0.9988 | likely_pathogenic | 0.999 | pathogenic | -1.928 | Destabilizing | 0.999 | D | 0.764 | deleterious | None | None | None | None | N |
| P/L | 0.8421 | likely_pathogenic | 0.8328 | pathogenic | -0.807 | Destabilizing | 0.978 | D | 0.783 | deleterious | D | 0.605536757 | None | None | N |
| P/M | 0.9752 | likely_pathogenic | 0.9733 | pathogenic | -1.09 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| P/N | 0.9985 | likely_pathogenic | 0.9986 | pathogenic | -2.339 | Highly Destabilizing | 0.999 | D | 0.809 | deleterious | None | None | None | None | N |
| P/Q | 0.9953 | likely_pathogenic | 0.9954 | pathogenic | -2.176 | Highly Destabilizing | 0.999 | D | 0.773 | deleterious | None | None | None | None | N |
| P/R | 0.9952 | likely_pathogenic | 0.9959 | pathogenic | -1.749 | Destabilizing | 0.999 | D | 0.805 | deleterious | D | 0.605738561 | None | None | N |
| P/S | 0.9788 | likely_pathogenic | 0.9763 | pathogenic | -2.919 | Highly Destabilizing | 0.989 | D | 0.738 | prob.delet. | D | 0.605536757 | None | None | N |
| P/T | 0.9219 | likely_pathogenic | 0.9216 | pathogenic | -2.553 | Highly Destabilizing | 0.989 | D | 0.743 | deleterious | D | 0.5897192 | None | None | N |
| P/V | 0.6582 | likely_pathogenic | 0.6459 | pathogenic | -1.283 | Destabilizing | 0.983 | D | 0.762 | deleterious | None | None | None | None | N |
| P/W | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -1.873 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| P/Y | 0.9994 | likely_pathogenic | 0.9994 | pathogenic | -1.539 | Destabilizing | 0.999 | D | 0.859 | 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.