Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9330 | 28213;28214;28215 | chr2:178711248;178711247;178711246 | chr2:179575975;179575974;179575973 |
| N2AB | 9013 | 27262;27263;27264 | chr2:178711248;178711247;178711246 | chr2:179575975;179575974;179575973 |
| N2A | 8086 | 24481;24482;24483 | chr2:178711248;178711247;178711246 | chr2:179575975;179575974;179575973 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs370277987  |
-1.447 | 0.012 | None | 0.427 | 0.084 | None | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| I/M | rs370277987 |
-1.447 | 0.012 | None | 0.427 | 0.084 | None | 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 |
| I/M | rs370277987 |
-1.447 | 0.012 | None | 0.427 | 0.084 | None | gnomAD-4.0.0 | 1.79707E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.45805E-05 | 0 | 0 |
| I/V | rs768696299 |
-1.687 | None | None | 0.151 | 0.087 | None | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 1.23998E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs768696299 |
-1.687 | None | None | 0.151 | 0.087 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 9.66E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs768696299 |
-1.687 | None | None | 0.151 | 0.087 | None | gnomAD-4.0.0 | 5.57706E-06 | None | None | None | None | N | None | 1.06806E-04 | 1.66694E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.6534 | likely_pathogenic | 0.6896 | pathogenic | -2.345 | Highly Destabilizing | 0.035 | N | 0.538 | neutral | None | None | None | None | N |
| I/C | 0.9007 | likely_pathogenic | 0.9123 | pathogenic | -1.611 | Destabilizing | 0.824 | D | 0.611 | neutral | None | None | None | None | N |
| I/D | 0.96 | likely_pathogenic | 0.9723 | pathogenic | -2.02 | Highly Destabilizing | 0.555 | D | 0.707 | prob.neutral | None | None | None | None | N |
| I/E | 0.9147 | likely_pathogenic | 0.9421 | pathogenic | -1.897 | Destabilizing | 0.555 | D | 0.69 | prob.neutral | None | None | None | None | N |
| I/F | 0.2635 | likely_benign | 0.3376 | benign | -1.511 | Destabilizing | 0.001 | N | 0.351 | neutral | None | None | None | None | N |
| I/G | 0.9088 | likely_pathogenic | 0.9338 | pathogenic | -2.814 | Highly Destabilizing | 0.555 | D | 0.7 | prob.neutral | None | None | None | None | N |
| I/H | 0.8631 | likely_pathogenic | 0.9065 | pathogenic | -2.112 | Highly Destabilizing | 0.935 | D | 0.637 | neutral | None | None | None | None | N |
| I/K | 0.7739 | likely_pathogenic | 0.8427 | pathogenic | -1.661 | Destabilizing | 0.555 | D | 0.695 | prob.neutral | None | None | None | None | N |
| I/L | 0.0964 | likely_benign | 0.1166 | benign | -1.043 | Destabilizing | None | N | 0.132 | neutral | None | None | None | None | N |
| I/M | 0.1635 | likely_benign | 0.1848 | benign | -0.891 | Destabilizing | 0.012 | N | 0.427 | neutral | None | None | None | None | N |
| I/N | 0.7076 | likely_pathogenic | 0.7685 | pathogenic | -1.657 | Destabilizing | 0.741 | D | 0.697 | prob.neutral | None | None | None | None | N |
| I/P | 0.8391 | likely_pathogenic | 0.8783 | pathogenic | -1.451 | Destabilizing | 0.791 | D | 0.698 | prob.neutral | None | None | None | None | N |
| I/Q | 0.8181 | likely_pathogenic | 0.87 | pathogenic | -1.685 | Destabilizing | 0.555 | D | 0.685 | prob.neutral | None | None | None | None | N |
| I/R | 0.681 | likely_pathogenic | 0.775 | pathogenic | -1.222 | Destabilizing | 0.555 | D | 0.704 | prob.neutral | None | None | None | None | N |
| I/S | 0.7184 | likely_pathogenic | 0.7653 | pathogenic | -2.396 | Highly Destabilizing | 0.317 | N | 0.651 | neutral | None | None | None | None | N |
| I/T | 0.676 | likely_pathogenic | 0.6942 | pathogenic | -2.132 | Highly Destabilizing | 0.062 | N | 0.64 | neutral | None | None | None | None | N |
| I/V | 0.095 | likely_benign | 0.0944 | benign | -1.451 | Destabilizing | None | N | 0.151 | neutral | None | None | None | None | N |
| I/W | 0.9255 | likely_pathogenic | 0.9603 | pathogenic | -1.714 | Destabilizing | 0.935 | D | 0.645 | neutral | None | None | None | None | N |
| I/Y | 0.7172 | likely_pathogenic | 0.8023 | pathogenic | -1.48 | Destabilizing | 0.235 | N | 0.675 | prob.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.