Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30947 | 93064;93065;93066 | chr2:178548787;178548786;178548785 | chr2:179413514;179413513;179413512 |
| N2AB | 29306 | 88141;88142;88143 | chr2:178548787;178548786;178548785 | chr2:179413514;179413513;179413512 |
| N2A | 28379 | 85360;85361;85362 | chr2:178548787;178548786;178548785 | chr2:179413514;179413513;179413512 |
| N2B | 21882 | 65869;65870;65871 | chr2:178548787;178548786;178548785 | chr2:179413514;179413513;179413512 |
| Novex-1 | 22007 | 66244;66245;66246 | chr2:178548787;178548786;178548785 | chr2:179413514;179413513;179413512 |
| Novex-2 | 22074 | 66445;66446;66447 | chr2:178548787;178548786;178548785 | chr2:179413514;179413513;179413512 |
| 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/T | rs566234008  |
-1.807 | 0.989 | N | 0.75 | 0.445 | 0.52535981233 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| I/T | rs566234008 |
-1.807 | 0.989 | N | 0.75 | 0.445 | 0.52535981233 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| I/T | rs566234008 |
-1.807 | 0.989 | N | 0.75 | 0.445 | 0.52535981233 | gnomAD-4.0.0 | 3.71998E-06 | None | None | None | None | N | None | 1.33454E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23803E-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 | 0.5021 | ambiguous | 0.4782 | ambiguous | -1.457 | Destabilizing | 0.992 | D | 0.707 | prob.neutral | None | None | None | None | N |
| I/C | 0.8528 | likely_pathogenic | 0.8355 | pathogenic | -0.801 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| I/D | 0.9948 | likely_pathogenic | 0.9942 | pathogenic | -1.857 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| I/E | 0.9889 | likely_pathogenic | 0.9886 | pathogenic | -1.601 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| I/F | 0.4317 | ambiguous | 0.4444 | ambiguous | -0.998 | Destabilizing | 0.998 | D | 0.729 | prob.delet. | N | 0.453147673 | None | None | N |
| I/G | 0.9465 | likely_pathogenic | 0.9391 | pathogenic | -1.918 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| I/H | 0.9737 | likely_pathogenic | 0.9734 | pathogenic | -1.767 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| I/K | 0.9729 | likely_pathogenic | 0.9747 | pathogenic | -0.946 | Destabilizing | 1.0 | D | 0.846 | deleterious | None | None | None | None | N |
| I/L | 0.1843 | likely_benign | 0.1801 | benign | -0.102 | Destabilizing | 0.889 | D | 0.519 | neutral | N | 0.452133715 | None | None | N |
| I/M | 0.2085 | likely_benign | 0.211 | benign | -0.279 | Destabilizing | 0.998 | D | 0.689 | prob.neutral | N | 0.460149112 | None | None | N |
| I/N | 0.9507 | likely_pathogenic | 0.9482 | pathogenic | -1.514 | Destabilizing | 0.999 | D | 0.839 | deleterious | N | 0.471758907 | None | None | N |
| I/P | 0.958 | likely_pathogenic | 0.9549 | pathogenic | -0.542 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| I/Q | 0.9688 | likely_pathogenic | 0.9687 | pathogenic | -1.157 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| I/R | 0.9495 | likely_pathogenic | 0.9497 | pathogenic | -1.292 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| I/S | 0.776 | likely_pathogenic | 0.7473 | pathogenic | -1.989 | Destabilizing | 0.998 | D | 0.797 | deleterious | N | 0.459895623 | None | None | N |
| I/T | 0.4422 | ambiguous | 0.4119 | ambiguous | -1.581 | Destabilizing | 0.989 | D | 0.75 | deleterious | N | 0.509349525 | None | None | N |
| I/V | 0.0936 | likely_benign | 0.0907 | benign | -0.542 | Destabilizing | 0.333 | N | 0.297 | neutral | N | 0.377744903 | None | None | N |
| I/W | 0.9713 | likely_pathogenic | 0.9725 | pathogenic | -1.288 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| I/Y | 0.9355 | likely_pathogenic | 0.9371 | pathogenic | -0.969 | Destabilizing | 1.0 | D | 0.755 | 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.