Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29897 | 89914;89915;89916 | chr2:178553211;178553210;178553209 | chr2:179417938;179417937;179417936 |
| N2AB | 28256 | 84991;84992;84993 | chr2:178553211;178553210;178553209 | chr2:179417938;179417937;179417936 |
| N2A | 27329 | 82210;82211;82212 | chr2:178553211;178553210;178553209 | chr2:179417938;179417937;179417936 |
| N2B | 20832 | 62719;62720;62721 | chr2:178553211;178553210;178553209 | chr2:179417938;179417937;179417936 |
| Novex-1 | 20957 | 63094;63095;63096 | chr2:178553211;178553210;178553209 | chr2:179417938;179417937;179417936 |
| Novex-2 | 21024 | 63295;63296;63297 | chr2:178553211;178553210;178553209 | chr2:179417938;179417937;179417936 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs180798672  |
-1.546 | 0.997 | N | 0.812 | 0.65 | None | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 1.15882E-04 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| L/F | rs180798672 |
-1.546 | 0.997 | N | 0.812 | 0.65 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| L/F | rs180798672 |
-1.546 | 0.997 | N | 0.812 | 0.65 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| L/F | rs180798672 |
-1.546 | 0.997 | N | 0.812 | 0.65 | None | gnomAD-4.0.0 | 1.11535E-05 | None | None | None | None | N | None | 0 | 6.66422E-05 | None | 0 | 0 | None | 0 | 0 | 1.18662E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9439 | likely_pathogenic | 0.9451 | pathogenic | -2.36 | Highly Destabilizing | 0.966 | D | 0.723 | prob.delet. | None | None | None | None | N |
| L/C | 0.8993 | likely_pathogenic | 0.9025 | pathogenic | -1.674 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| L/D | 0.9995 | likely_pathogenic | 0.9994 | pathogenic | -2.907 | Highly Destabilizing | 0.999 | D | 0.899 | deleterious | None | None | None | None | N |
| L/E | 0.9955 | likely_pathogenic | 0.9954 | pathogenic | -2.568 | Highly Destabilizing | 0.998 | D | 0.887 | deleterious | None | None | None | None | N |
| L/F | 0.506 | ambiguous | 0.4526 | ambiguous | -1.425 | Destabilizing | 0.997 | D | 0.812 | deleterious | N | 0.513798488 | None | None | N |
| L/G | 0.9913 | likely_pathogenic | 0.9914 | pathogenic | -2.99 | Highly Destabilizing | 0.998 | D | 0.886 | deleterious | None | None | None | None | N |
| L/H | 0.9829 | likely_pathogenic | 0.9819 | pathogenic | -2.839 | Highly Destabilizing | 1.0 | D | 0.868 | deleterious | D | 0.582647564 | None | None | N |
| L/I | 0.2044 | likely_benign | 0.2031 | benign | -0.469 | Destabilizing | 0.955 | D | 0.716 | prob.delet. | D | 0.534015884 | None | None | N |
| L/K | 0.9904 | likely_pathogenic | 0.9904 | pathogenic | -1.793 | Destabilizing | 0.998 | D | 0.876 | deleterious | None | None | None | None | N |
| L/M | 0.2925 | likely_benign | 0.2914 | benign | -0.67 | Destabilizing | 0.998 | D | 0.805 | deleterious | None | None | None | None | N |
| L/N | 0.9967 | likely_pathogenic | 0.9967 | pathogenic | -2.534 | Highly Destabilizing | 0.999 | D | 0.898 | deleterious | None | None | None | None | N |
| L/P | 0.9967 | likely_pathogenic | 0.9963 | pathogenic | -1.089 | Destabilizing | 0.999 | D | 0.897 | deleterious | D | 0.582647564 | None | None | N |
| L/Q | 0.9749 | likely_pathogenic | 0.9749 | pathogenic | -2.097 | Highly Destabilizing | 0.999 | D | 0.892 | deleterious | None | None | None | None | N |
| L/R | 0.9806 | likely_pathogenic | 0.9799 | pathogenic | -2.066 | Highly Destabilizing | 0.999 | D | 0.895 | deleterious | D | 0.582647564 | None | None | N |
| L/S | 0.9938 | likely_pathogenic | 0.9937 | pathogenic | -3.119 | Highly Destabilizing | 0.998 | D | 0.871 | deleterious | None | None | None | None | N |
| L/T | 0.9785 | likely_pathogenic | 0.9792 | pathogenic | -2.594 | Highly Destabilizing | 0.995 | D | 0.805 | deleterious | None | None | None | None | N |
| L/V | 0.2656 | likely_benign | 0.2694 | benign | -1.089 | Destabilizing | 0.117 | N | 0.451 | neutral | N | 0.521952016 | None | None | N |
| L/W | 0.935 | likely_pathogenic | 0.9206 | pathogenic | -1.793 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| L/Y | 0.9471 | likely_pathogenic | 0.9389 | pathogenic | -1.537 | Destabilizing | 0.999 | D | 0.821 | 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.