Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33671 | 101236;101237;101238 | chr2:178535604;178535603;178535602 | chr2:179400331;179400330;179400329 |
| N2AB | 32030 | 96313;96314;96315 | chr2:178535604;178535603;178535602 | chr2:179400331;179400330;179400329 |
| N2A | 31103 | 93532;93533;93534 | chr2:178535604;178535603;178535602 | chr2:179400331;179400330;179400329 |
| N2B | 24606 | 74041;74042;74043 | chr2:178535604;178535603;178535602 | chr2:179400331;179400330;179400329 |
| Novex-1 | 24731 | 74416;74417;74418 | chr2:178535604;178535603;178535602 | chr2:179400331;179400330;179400329 |
| Novex-2 | 24798 | 74617;74618;74619 | chr2:178535604;178535603;178535602 | chr2:179400331;179400330;179400329 |
| 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/D | rs1575296563  |
None | 1.0 | D | 0.875 | 0.808 | 0.881265930199 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/D | rs1575296563 |
None | 1.0 | D | 0.875 | 0.808 | 0.881265930199 | gnomAD-4.0.0 | 6.57263E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47037E-05 | 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 | 0.873 | likely_pathogenic | 0.81 | pathogenic | -1.092 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| A/D | 0.9995 | likely_pathogenic | 0.9984 | pathogenic | -2.17 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | D | 0.602782936 | None | None | N |
| A/E | 0.9985 | likely_pathogenic | 0.9947 | pathogenic | -2.072 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| A/F | 0.9943 | likely_pathogenic | 0.9796 | pathogenic | -0.865 | Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | None | N |
| A/G | 0.706 | likely_pathogenic | 0.6128 | pathogenic | -1.394 | Destabilizing | 1.0 | D | 0.565 | neutral | D | 0.557339385 | None | None | N |
| A/H | 0.999 | likely_pathogenic | 0.9972 | pathogenic | -1.918 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| A/I | 0.9485 | likely_pathogenic | 0.8444 | pathogenic | -0.027 | Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| A/K | 0.9995 | likely_pathogenic | 0.9984 | pathogenic | -1.292 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| A/L | 0.9042 | likely_pathogenic | 0.7715 | pathogenic | -0.027 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| A/M | 0.9706 | likely_pathogenic | 0.9092 | pathogenic | -0.128 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| A/N | 0.998 | likely_pathogenic | 0.9943 | pathogenic | -1.311 | Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| A/P | 0.9979 | likely_pathogenic | 0.9941 | pathogenic | -0.31 | Destabilizing | 1.0 | D | 0.879 | deleterious | D | 0.602581132 | None | None | N |
| A/Q | 0.9947 | likely_pathogenic | 0.9872 | pathogenic | -1.276 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| A/R | 0.9965 | likely_pathogenic | 0.9911 | pathogenic | -1.228 | Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| A/S | 0.6073 | likely_pathogenic | 0.5056 | ambiguous | -1.648 | Destabilizing | 1.0 | D | 0.571 | neutral | D | 0.602177523 | None | None | N |
| A/T | 0.8633 | likely_pathogenic | 0.6765 | pathogenic | -1.446 | Destabilizing | 1.0 | D | 0.779 | deleterious | D | 0.601975719 | None | None | N |
| A/V | 0.7987 | likely_pathogenic | 0.5753 | pathogenic | -0.31 | Destabilizing | 1.0 | D | 0.647 | neutral | D | 0.531411679 | None | None | N |
| A/W | 0.9997 | likely_pathogenic | 0.9991 | pathogenic | -1.549 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| A/Y | 0.9987 | likely_pathogenic | 0.9957 | pathogenic | -1.03 | Destabilizing | 1.0 | D | 0.883 | 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.