Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20935 | 63028;63029;63030 | chr2:178588922;178588921;178588920 | chr2:179453649;179453648;179453647 |
| N2AB | 19294 | 58105;58106;58107 | chr2:178588922;178588921;178588920 | chr2:179453649;179453648;179453647 |
| N2A | 18367 | 55324;55325;55326 | chr2:178588922;178588921;178588920 | chr2:179453649;179453648;179453647 |
| N2B | 11870 | 35833;35834;35835 | chr2:178588922;178588921;178588920 | chr2:179453649;179453648;179453647 |
| Novex-1 | 11995 | 36208;36209;36210 | chr2:178588922;178588921;178588920 | chr2:179453649;179453648;179453647 |
| Novex-2 | 12062 | 36409;36410;36411 | chr2:178588922;178588921;178588920 | chr2:179453649;179453648;179453647 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/V | rs1249633842  |
-1.558 | 0.993 | N | 0.407 | 0.16 | 0.600074432338 | gnomAD-2.1.1 | 6.38E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.29634E-04 | 0 |
| I/V | rs1249633842 |
-1.558 | 0.993 | N | 0.407 | 0.16 | 0.600074432338 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/V | rs1249633842 |
-1.558 | 0.993 | N | 0.407 | 0.16 | 0.600074432338 | gnomAD-4.0.0 | 3.84737E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.18401E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5402 | ambiguous | 0.5764 | pathogenic | -2.395 | Highly Destabilizing | 0.999 | D | 0.632 | neutral | None | None | None | None | N |
| I/C | 0.6715 | likely_pathogenic | 0.6867 | pathogenic | -1.451 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| I/D | 0.9329 | likely_pathogenic | 0.9434 | pathogenic | -2.872 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| I/E | 0.8097 | likely_pathogenic | 0.8226 | pathogenic | -2.617 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| I/F | 0.281 | likely_benign | 0.3053 | benign | -1.343 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | N | 0.453160674 | None | None | N |
| I/G | 0.8293 | likely_pathogenic | 0.8562 | pathogenic | -2.937 | Highly Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| I/H | 0.6542 | likely_pathogenic | 0.6772 | pathogenic | -2.567 | Highly Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| I/K | 0.5858 | likely_pathogenic | 0.6028 | pathogenic | -1.58 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| I/L | 0.1165 | likely_benign | 0.1158 | benign | -0.802 | Destabilizing | 0.993 | D | 0.405 | neutral | N | 0.491062914 | None | None | N |
| I/M | 0.1463 | likely_benign | 0.1547 | benign | -0.829 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.503973496 | None | None | N |
| I/N | 0.5173 | ambiguous | 0.5371 | ambiguous | -2.019 | Highly Destabilizing | 1.0 | D | 0.84 | deleterious | N | 0.46445257 | None | None | N |
| I/P | 0.991 | likely_pathogenic | 0.9943 | pathogenic | -1.319 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| I/Q | 0.5708 | likely_pathogenic | 0.5707 | pathogenic | -1.806 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| I/R | 0.477 | ambiguous | 0.5047 | ambiguous | -1.489 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| I/S | 0.4742 | ambiguous | 0.5032 | ambiguous | -2.623 | Highly Destabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.488251895 | None | None | N |
| I/T | 0.3213 | likely_benign | 0.3654 | ambiguous | -2.231 | Highly Destabilizing | 1.0 | D | 0.73 | prob.delet. | N | 0.478861621 | None | None | N |
| I/V | 0.0762 | likely_benign | 0.0812 | benign | -1.319 | Destabilizing | 0.993 | D | 0.407 | neutral | N | 0.491734918 | None | None | N |
| I/W | 0.8878 | likely_pathogenic | 0.9059 | pathogenic | -1.817 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| I/Y | 0.6435 | likely_pathogenic | 0.6631 | pathogenic | -1.523 | Destabilizing | 1.0 | D | 0.764 | 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.