Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18781 | 56566;56567;56568 | chr2:178599560;178599559;178599558 | chr2:179464287;179464286;179464285 |
| N2AB | 17140 | 51643;51644;51645 | chr2:178599560;178599559;178599558 | chr2:179464287;179464286;179464285 |
| N2A | 16213 | 48862;48863;48864 | chr2:178599560;178599559;178599558 | chr2:179464287;179464286;179464285 |
| N2B | 9716 | 29371;29372;29373 | chr2:178599560;178599559;178599558 | chr2:179464287;179464286;179464285 |
| Novex-1 | 9841 | 29746;29747;29748 | chr2:178599560;178599559;178599558 | chr2:179464287;179464286;179464285 |
| Novex-2 | 9908 | 29947;29948;29949 | chr2:178599560;178599559;178599558 | chr2:179464287;179464286;179464285 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/D | None | None | 0.999 | D | 0.647 | 0.904 | 0.938300441422 | gnomAD-4.0.0 | 1.72885E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.07014E-06 | 0 | 0 |
| V/F | rs2052720429  |
None | 0.997 | D | 0.645 | 0.724 | 0.919627025024 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78927E-04 |
| V/F | rs2052720429 |
None | 0.997 | D | 0.645 | 0.724 | 0.919627025024 | gnomAD-4.0.0 | 6.57626E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78927E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.9327 | likely_pathogenic | 0.9318 | pathogenic | -1.928 | Destabilizing | 0.978 | D | 0.609 | neutral | D | 0.605517115 | None | None | N |
| V/C | 0.9661 | likely_pathogenic | 0.9668 | pathogenic | -2.044 | Highly Destabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | N |
| V/D | 0.996 | likely_pathogenic | 0.9954 | pathogenic | -3.043 | Highly Destabilizing | 0.999 | D | 0.647 | neutral | D | 0.622141888 | None | None | N |
| V/E | 0.9931 | likely_pathogenic | 0.9918 | pathogenic | -2.957 | Highly Destabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | N |
| V/F | 0.9217 | likely_pathogenic | 0.9118 | pathogenic | -1.302 | Destabilizing | 0.997 | D | 0.645 | neutral | D | 0.621536476 | None | None | N |
| V/G | 0.9558 | likely_pathogenic | 0.9524 | pathogenic | -2.28 | Highly Destabilizing | 0.999 | D | 0.62 | neutral | D | 0.622141888 | None | None | N |
| V/H | 0.9967 | likely_pathogenic | 0.9964 | pathogenic | -1.623 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| V/I | 0.1066 | likely_benign | 0.1014 | benign | -1.001 | Destabilizing | 0.37 | N | 0.479 | neutral | N | 0.512906063 | None | None | N |
| V/K | 0.993 | likely_pathogenic | 0.9927 | pathogenic | -1.625 | Destabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | N |
| V/L | 0.8578 | likely_pathogenic | 0.8485 | pathogenic | -1.001 | Destabilizing | 0.9 | D | 0.626 | neutral | D | 0.57796096 | None | None | N |
| V/M | 0.8452 | likely_pathogenic | 0.8276 | pathogenic | -1.264 | Destabilizing | 0.998 | D | 0.687 | prob.neutral | None | None | None | None | N |
| V/N | 0.9773 | likely_pathogenic | 0.9762 | pathogenic | -1.838 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| V/P | 0.9907 | likely_pathogenic | 0.9902 | pathogenic | -1.283 | Destabilizing | 0.999 | D | 0.623 | neutral | None | None | None | None | N |
| V/Q | 0.9919 | likely_pathogenic | 0.9914 | pathogenic | -1.969 | Destabilizing | 0.999 | D | 0.632 | neutral | None | None | None | None | N |
| V/R | 0.988 | likely_pathogenic | 0.9872 | pathogenic | -1.159 | Destabilizing | 0.999 | D | 0.652 | neutral | None | None | None | None | N |
| V/S | 0.9565 | likely_pathogenic | 0.953 | pathogenic | -2.286 | Highly Destabilizing | 0.999 | D | 0.591 | neutral | None | None | None | None | N |
| V/T | 0.8858 | likely_pathogenic | 0.882 | pathogenic | -2.095 | Highly Destabilizing | 0.992 | D | 0.649 | neutral | None | None | None | None | N |
| V/W | 0.9991 | likely_pathogenic | 0.9989 | pathogenic | -1.568 | Destabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | N |
| V/Y | 0.9924 | likely_pathogenic | 0.9918 | pathogenic | -1.279 | Destabilizing | 0.999 | D | 0.65 | neutral | 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.