Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4869 | 14830;14831;14832 | chr2:178735841;178735840;178735839 | chr2:179600568;179600567;179600566 |
| N2AB | 4552 | 13879;13880;13881 | chr2:178735841;178735840;178735839 | chr2:179600568;179600567;179600566 |
| N2A | 3625 | 11098;11099;11100 | chr2:178735841;178735840;178735839 | chr2:179600568;179600567;179600566 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | rs768296194  |
-0.86 | 1.0 | D | 0.882 | 0.769 | 0.659973416392 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| A/P | rs768296194 |
-0.86 | 1.0 | D | 0.882 | 0.769 | 0.659973416392 | gnomAD-4.0.0 | 2.05268E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69839E-06 | 0 | 0 |
| A/S | rs768296194 |
None | 0.998 | D | 0.616 | 0.681 | 0.558264529485 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/S | rs768296194 |
None | 0.998 | D | 0.616 | 0.681 | 0.558264529485 | gnomAD-4.0.0 | 1.85913E-06 | None | None | None | None | N | None | 1.33479E-05 | 1.66711E-05 | None | 0 | 0 | None | 0 | 0 | 8.47597E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.8905 | likely_pathogenic | 0.8816 | pathogenic | -1.516 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| A/D | 0.9928 | likely_pathogenic | 0.9921 | pathogenic | -2.799 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | D | 0.818989187 | None | None | N |
| A/E | 0.9853 | likely_pathogenic | 0.9861 | pathogenic | -2.646 | Highly Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| A/F | 0.9462 | likely_pathogenic | 0.9424 | pathogenic | -0.879 | Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| A/G | 0.4752 | ambiguous | 0.4027 | ambiguous | -1.776 | Destabilizing | 0.999 | D | 0.608 | neutral | D | 0.69022173 | None | None | N |
| A/H | 0.9945 | likely_pathogenic | 0.9938 | pathogenic | -2.058 | Highly Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | N |
| A/I | 0.5838 | likely_pathogenic | 0.6566 | pathogenic | -0.225 | Destabilizing | 0.994 | D | 0.748 | deleterious | None | None | None | None | N |
| A/K | 0.9968 | likely_pathogenic | 0.997 | pathogenic | -1.507 | Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| A/L | 0.6971 | likely_pathogenic | 0.7204 | pathogenic | -0.225 | Destabilizing | 0.994 | D | 0.686 | prob.neutral | None | None | None | None | N |
| A/M | 0.8338 | likely_pathogenic | 0.8398 | pathogenic | -0.457 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| A/N | 0.9813 | likely_pathogenic | 0.9795 | pathogenic | -1.745 | Destabilizing | 1.0 | D | 0.885 | deleterious | None | None | None | None | N |
| A/P | 0.9876 | likely_pathogenic | 0.9851 | pathogenic | -0.56 | Destabilizing | 1.0 | D | 0.882 | deleterious | D | 0.785161865 | None | None | N |
| A/Q | 0.9839 | likely_pathogenic | 0.9838 | pathogenic | -1.637 | Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | None | N |
| A/R | 0.9889 | likely_pathogenic | 0.9891 | pathogenic | -1.437 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| A/S | 0.4017 | ambiguous | 0.3646 | ambiguous | -2.101 | Highly Destabilizing | 0.998 | D | 0.616 | neutral | D | 0.736614226 | None | None | N |
| A/T | 0.5032 | ambiguous | 0.5032 | ambiguous | -1.843 | Destabilizing | 0.996 | D | 0.683 | prob.neutral | D | 0.76472977 | None | None | N |
| A/V | 0.2508 | likely_benign | 0.2984 | benign | -0.56 | Destabilizing | 0.884 | D | 0.397 | neutral | D | 0.570204992 | None | None | N |
| A/W | 0.9976 | likely_pathogenic | 0.9972 | pathogenic | -1.601 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| A/Y | 0.9848 | likely_pathogenic | 0.983 | pathogenic | -1.138 | Destabilizing | 1.0 | D | 0.905 | 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.