Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35957 | 108094;108095;108096 | chr2:178527119;178527118;178527117 | chr2:179391846;179391845;179391844 |
| N2AB | 34316 | 103171;103172;103173 | chr2:178527119;178527118;178527117 | chr2:179391846;179391845;179391844 |
| N2A | 33389 | 100390;100391;100392 | chr2:178527119;178527118;178527117 | chr2:179391846;179391845;179391844 |
| N2B | 26892 | 80899;80900;80901 | chr2:178527119;178527118;178527117 | chr2:179391846;179391845;179391844 |
| Novex-1 | 27017 | 81274;81275;81276 | chr2:178527119;178527118;178527117 | chr2:179391846;179391845;179391844 |
| Novex-2 | 27084 | 81475;81476;81477 | chr2:178527119;178527118;178527117 | chr2:179391846;179391845;179391844 |
| 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/F | rs950902715  |
-1.717 | 0.071 | N | 0.453 | 0.274 | 0.46017455471 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | -0.247(OBSL1) -0.452(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.85E-06 | 0 |
| I/F | rs950902715 |
-1.717 | 0.071 | N | 0.453 | 0.274 | 0.46017455471 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | -0.247(OBSL1) -0.452(OBSCN) | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/F | rs950902715 |
-1.717 | 0.071 | N | 0.453 | 0.274 | 0.46017455471 | gnomAD-4.0.0 | 2.91226E-05 | None | None | None | -0.247(OBSL1) -0.452(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.98348E-05 | 0 | 0 |
| I/M | None | None | 0.998 | D | 0.614 | 0.286 | 0.646296243553 | gnomAD-4.0.0 | 6.84147E-07 | None | None | None | -0.749(OBSL1) -0.739(OBSCN) | N | None | 0 | 0 | None | 0 | 2.51927E-05 | 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 | 0.9275 | likely_pathogenic | 0.9407 | pathogenic | -2.547 | Highly Destabilizing | 0.942 | D | 0.602 | neutral | None | None | None | -0.072(OBSL1) -0.373(OBSCN) | N |
| I/C | 0.9552 | likely_pathogenic | 0.9643 | pathogenic | -1.79 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | -0.969(OBSL1) -0.907(OBSCN) | N |
| I/D | 0.9863 | likely_pathogenic | 0.9886 | pathogenic | -2.741 | Highly Destabilizing | 0.996 | D | 0.719 | prob.delet. | None | None | None | -0.912(OBSL1) -0.672(OBSCN) | N |
| I/E | 0.9527 | likely_pathogenic | 0.959 | pathogenic | -2.59 | Highly Destabilizing | 0.996 | D | 0.719 | prob.delet. | None | None | None | -1.078(OBSL1) -0.826(OBSCN) | N |
| I/F | 0.6059 | likely_pathogenic | 0.6697 | pathogenic | -1.549 | Destabilizing | 0.071 | N | 0.453 | neutral | N | 0.475088676 | None | -0.247(OBSL1) -0.452(OBSCN) | N |
| I/G | 0.9837 | likely_pathogenic | 0.986 | pathogenic | -3.017 | Highly Destabilizing | 0.991 | D | 0.693 | prob.neutral | None | None | None | 0.01(OBSL1) -0.281(OBSCN) | N |
| I/H | 0.9221 | likely_pathogenic | 0.9329 | pathogenic | -2.349 | Highly Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | 0.137(OBSL1) -0.001(OBSCN) | N |
| I/K | 0.8895 | likely_pathogenic | 0.8963 | pathogenic | -2.047 | Highly Destabilizing | 0.991 | D | 0.721 | prob.delet. | None | None | None | -0.887(OBSL1) -1.085(OBSCN) | N |
| I/L | 0.3562 | ambiguous | 0.3978 | ambiguous | -1.22 | Destabilizing | 0.689 | D | 0.441 | neutral | N | 0.459119146 | None | -0.398(OBSL1) -0.701(OBSCN) | N |
| I/M | 0.2911 | likely_benign | 0.3373 | benign | -1.089 | Destabilizing | 0.998 | D | 0.614 | neutral | D | 0.52769101 | None | -0.749(OBSL1) -0.739(OBSCN) | N |
| I/N | 0.8667 | likely_pathogenic | 0.8859 | pathogenic | -2.182 | Highly Destabilizing | 0.989 | D | 0.723 | prob.delet. | N | 0.494194512 | None | -0.443(OBSL1) -0.713(OBSCN) | N |
| I/P | 0.9977 | likely_pathogenic | 0.9977 | pathogenic | -1.641 | Destabilizing | 0.996 | D | 0.734 | prob.delet. | None | None | None | -0.277(OBSL1) -0.585(OBSCN) | N |
| I/Q | 0.8969 | likely_pathogenic | 0.9058 | pathogenic | -2.174 | Highly Destabilizing | 0.996 | D | 0.747 | deleterious | None | None | None | -0.563(OBSL1) -0.781(OBSCN) | N |
| I/R | 0.8291 | likely_pathogenic | 0.8389 | pathogenic | -1.552 | Destabilizing | 0.996 | D | 0.733 | prob.delet. | None | None | None | -0.869(OBSL1) -0.993(OBSCN) | N |
| I/S | 0.8883 | likely_pathogenic | 0.9036 | pathogenic | -2.84 | Highly Destabilizing | 0.925 | D | 0.628 | neutral | N | 0.494578514 | None | -0.135(OBSL1) -0.439(OBSCN) | N |
| I/T | 0.8122 | likely_pathogenic | 0.8527 | pathogenic | -2.567 | Highly Destabilizing | 0.248 | N | 0.434 | neutral | N | 0.432468475 | None | -0.293(OBSL1) -0.595(OBSCN) | N |
| I/V | 0.2179 | likely_benign | 0.2682 | benign | -1.641 | Destabilizing | 0.835 | D | 0.448 | neutral | N | 0.464428965 | None | -0.277(OBSL1) -0.585(OBSCN) | N |
| I/W | 0.9682 | likely_pathogenic | 0.9749 | pathogenic | -1.873 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | -0.622(OBSL1) -0.689(OBSCN) | N |
| I/Y | 0.8962 | likely_pathogenic | 0.9078 | pathogenic | -1.642 | Destabilizing | 0.983 | D | 0.629 | neutral | None | None | None | -0.252(OBSL1) -0.505(OBSCN) | 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.