Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19594 | 59005;59006;59007 | chr2:178593428;178593427;178593426 | chr2:179458155;179458154;179458153 |
| N2AB | 17953 | 54082;54083;54084 | chr2:178593428;178593427;178593426 | chr2:179458155;179458154;179458153 |
| N2A | 17026 | 51301;51302;51303 | chr2:178593428;178593427;178593426 | chr2:179458155;179458154;179458153 |
| N2B | 10529 | 31810;31811;31812 | chr2:178593428;178593427;178593426 | chr2:179458155;179458154;179458153 |
| Novex-1 | 10654 | 32185;32186;32187 | chr2:178593428;178593427;178593426 | chr2:179458155;179458154;179458153 |
| Novex-2 | 10721 | 32386;32387;32388 | chr2:178593428;178593427;178593426 | chr2:179458155;179458154;179458153 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | None | None | 0.955 | N | 0.665 | 0.253 | 0.336155897331 | gnomAD-4.0.0 | 1.5927E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85986E-06 | 0 | 0 |
| D/N | rs2050669783  |
None | 0.235 | N | 0.331 | 0.087 | 0.184867976434 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs2050669783 |
None | 0.235 | N | 0.331 | 0.087 | 0.184867976434 | gnomAD-4.0.0 | 6.57601E-06 | None | None | None | None | N | None | 2.41394E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3186 | likely_benign | 0.2464 | benign | -0.347 | Destabilizing | 0.993 | D | 0.735 | prob.delet. | N | 0.493716228 | None | None | N |
| D/C | 0.7182 | likely_pathogenic | 0.6266 | pathogenic | 0.184 | Stabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| D/E | 0.1865 | likely_benign | 0.1856 | benign | -0.563 | Destabilizing | 0.977 | D | 0.451 | neutral | N | 0.487331962 | None | None | N |
| D/F | 0.6163 | likely_pathogenic | 0.555 | ambiguous | -0.668 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| D/G | 0.2632 | likely_benign | 0.2069 | benign | -0.559 | Destabilizing | 0.955 | D | 0.665 | neutral | N | 0.477409172 | None | None | N |
| D/H | 0.4025 | ambiguous | 0.316 | benign | -0.916 | Destabilizing | 0.999 | D | 0.696 | prob.neutral | N | 0.475776557 | None | None | N |
| D/I | 0.5259 | ambiguous | 0.4518 | ambiguous | 0.166 | Stabilizing | 0.998 | D | 0.762 | deleterious | None | None | None | None | N |
| D/K | 0.5649 | likely_pathogenic | 0.4869 | ambiguous | 0.16 | Stabilizing | 0.995 | D | 0.71 | prob.delet. | None | None | None | None | N |
| D/L | 0.5471 | ambiguous | 0.4647 | ambiguous | 0.166 | Stabilizing | 0.998 | D | 0.746 | deleterious | None | None | None | None | N |
| D/M | 0.6782 | likely_pathogenic | 0.615 | pathogenic | 0.618 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| D/N | 0.1173 | likely_benign | 0.0885 | benign | -0.029 | Destabilizing | 0.235 | N | 0.331 | neutral | N | 0.480941921 | None | None | N |
| D/P | 0.9731 | likely_pathogenic | 0.9552 | pathogenic | 0.017 | Stabilizing | 0.999 | D | 0.723 | prob.delet. | None | None | None | None | N |
| D/Q | 0.4604 | ambiguous | 0.392 | ambiguous | -0.028 | Destabilizing | 0.995 | D | 0.677 | prob.neutral | None | None | None | None | N |
| D/R | 0.6291 | likely_pathogenic | 0.5367 | ambiguous | 0.069 | Stabilizing | 0.995 | D | 0.731 | prob.delet. | None | None | None | None | N |
| D/S | 0.1997 | likely_benign | 0.147 | benign | -0.171 | Destabilizing | 0.966 | D | 0.605 | neutral | None | None | None | None | N |
| D/T | 0.2498 | likely_benign | 0.1976 | benign | -0.009 | Destabilizing | 0.995 | D | 0.716 | prob.delet. | None | None | None | None | N |
| D/V | 0.3543 | ambiguous | 0.2867 | benign | 0.017 | Stabilizing | 0.997 | D | 0.746 | deleterious | D | 0.528203218 | None | None | N |
| D/W | 0.9029 | likely_pathogenic | 0.8652 | pathogenic | -0.66 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| D/Y | 0.2426 | likely_benign | 0.1994 | benign | -0.458 | Destabilizing | 1.0 | D | 0.754 | deleterious | N | 0.487132863 | 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.