Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20927 | 63004;63005;63006 | chr2:178588946;178588945;178588944 | chr2:179453673;179453672;179453671 |
| N2AB | 19286 | 58081;58082;58083 | chr2:178588946;178588945;178588944 | chr2:179453673;179453672;179453671 |
| N2A | 18359 | 55300;55301;55302 | chr2:178588946;178588945;178588944 | chr2:179453673;179453672;179453671 |
| N2B | 11862 | 35809;35810;35811 | chr2:178588946;178588945;178588944 | chr2:179453673;179453672;179453671 |
| Novex-1 | 11987 | 36184;36185;36186 | chr2:178588946;178588945;178588944 | chr2:179453673;179453672;179453671 |
| Novex-2 | 12054 | 36385;36386;36387 | chr2:178588946;178588945;178588944 | chr2:179453673;179453672;179453671 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs547604540  |
0.002 | 1.0 | N | 0.651 | 0.451 | 0.661991603742 | gnomAD-2.1.1 | 1.44E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 2.36E-05 | 0 |
| R/C | rs547604540 |
0.002 | 1.0 | N | 0.651 | 0.451 | 0.661991603742 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs547604540 |
0.002 | 1.0 | N | 0.651 | 0.451 | 0.661991603742 | gnomAD-4.0.0 | 1.79839E-05 | None | None | None | None | N | None | 1.33586E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.3741E-05 | 0 | 0 |
| R/H | rs397517652 |
-0.765 | 0.132 | N | 0.165 | 0.178 | 0.166414681773 | gnomAD-2.1.1 | 1.08E-05 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| R/H | rs397517652 |
-0.765 | 0.132 | N | 0.165 | 0.178 | 0.166414681773 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 1.20802E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs397517652 |
-0.765 | 0.132 | N | 0.165 | 0.178 | 0.166414681773 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/H | rs397517652 |
-0.765 | 0.132 | N | 0.165 | 0.178 | 0.166414681773 | gnomAD-4.0.0 | 1.61224E-05 | None | None | None | None | N | None | 8.00406E-05 | 1.66995E-05 | None | 0 | 2.24266E-05 | None | 0 | 0 | 1.52622E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8018 | likely_pathogenic | 0.8638 | pathogenic | 0.095 | Stabilizing | 0.919 | D | 0.471 | neutral | None | None | None | None | N |
| R/C | 0.3892 | ambiguous | 0.4605 | ambiguous | -0.072 | Destabilizing | 1.0 | D | 0.651 | neutral | N | 0.476858832 | None | None | N |
| R/D | 0.8991 | likely_pathogenic | 0.9323 | pathogenic | -0.114 | Destabilizing | 0.976 | D | 0.478 | neutral | None | None | None | None | N |
| R/E | 0.8042 | likely_pathogenic | 0.8497 | pathogenic | -0.032 | Destabilizing | 0.919 | D | 0.453 | neutral | None | None | None | None | N |
| R/F | 0.8953 | likely_pathogenic | 0.9323 | pathogenic | -0.062 | Destabilizing | 0.988 | D | 0.605 | neutral | None | None | None | None | N |
| R/G | 0.5166 | ambiguous | 0.6079 | pathogenic | -0.119 | Destabilizing | 0.956 | D | 0.461 | neutral | N | 0.40212606 | None | None | N |
| R/H | 0.1726 | likely_benign | 0.1843 | benign | -0.711 | Destabilizing | 0.132 | N | 0.165 | neutral | N | 0.48165121 | None | None | N |
| R/I | 0.863 | likely_pathogenic | 0.8995 | pathogenic | 0.628 | Stabilizing | 0.988 | D | 0.594 | neutral | None | None | None | None | N |
| R/K | 0.196 | likely_benign | 0.2012 | benign | 0.031 | Stabilizing | 0.825 | D | 0.432 | neutral | None | None | None | None | N |
| R/L | 0.6775 | likely_pathogenic | 0.7439 | pathogenic | 0.628 | Stabilizing | 0.956 | D | 0.455 | neutral | N | 0.476605343 | None | None | N |
| R/M | 0.7725 | likely_pathogenic | 0.8177 | pathogenic | 0.072 | Stabilizing | 0.999 | D | 0.491 | neutral | None | None | None | None | N |
| R/N | 0.8032 | likely_pathogenic | 0.8701 | pathogenic | 0.184 | Stabilizing | 0.919 | D | 0.465 | neutral | None | None | None | None | N |
| R/P | 0.9279 | likely_pathogenic | 0.9447 | pathogenic | 0.472 | Stabilizing | 0.998 | D | 0.545 | neutral | N | 0.469261509 | None | None | N |
| R/Q | 0.271 | likely_benign | 0.3204 | benign | 0.146 | Stabilizing | 0.976 | D | 0.507 | neutral | None | None | None | None | N |
| R/S | 0.8239 | likely_pathogenic | 0.8735 | pathogenic | -0.097 | Destabilizing | 0.956 | D | 0.477 | neutral | N | 0.48751839 | None | None | N |
| R/T | 0.7935 | likely_pathogenic | 0.8471 | pathogenic | 0.128 | Stabilizing | 0.988 | D | 0.455 | neutral | None | None | None | None | N |
| R/V | 0.8646 | likely_pathogenic | 0.9036 | pathogenic | 0.472 | Stabilizing | 0.988 | D | 0.587 | neutral | None | None | None | None | N |
| R/W | 0.5049 | ambiguous | 0.5822 | pathogenic | -0.148 | Destabilizing | 0.999 | D | 0.673 | neutral | None | None | None | None | N |
| R/Y | 0.6856 | likely_pathogenic | 0.7776 | pathogenic | 0.265 | Stabilizing | 0.976 | D | 0.53 | 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.