Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20138 | 60637;60638;60639 | chr2:178591313;178591312;178591311 | chr2:179456040;179456039;179456038 |
| N2AB | 18497 | 55714;55715;55716 | chr2:178591313;178591312;178591311 | chr2:179456040;179456039;179456038 |
| N2A | 17570 | 52933;52934;52935 | chr2:178591313;178591312;178591311 | chr2:179456040;179456039;179456038 |
| N2B | 11073 | 33442;33443;33444 | chr2:178591313;178591312;178591311 | chr2:179456040;179456039;179456038 |
| Novex-1 | 11198 | 33817;33818;33819 | chr2:178591313;178591312;178591311 | chr2:179456040;179456039;179456038 |
| Novex-2 | 11265 | 34018;34019;34020 | chr2:178591313;178591312;178591311 | chr2:179456040;179456039;179456038 |
| 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/N | rs762525368  |
-3.117 | 0.997 | D | 0.885 | 0.748 | 0.931505991749 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| I/N | rs762525368 |
-3.117 | 0.997 | D | 0.885 | 0.748 | 0.931505991749 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/N | rs762525368 |
-3.117 | 0.997 | D | 0.885 | 0.748 | 0.931505991749 | gnomAD-4.0.0 | 3.40949E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.57833E-05 | 0 | 1.60143E-05 |
| I/T | rs762525368 |
None | 0.991 | D | 0.772 | 0.79 | 0.89323557897 | gnomAD-4.0.0 | 6.84393E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51953E-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 | 0.9394 | likely_pathogenic | 0.9496 | pathogenic | -2.946 | Highly Destabilizing | 0.953 | D | 0.711 | prob.delet. | None | None | None | None | N |
| I/C | 0.9575 | likely_pathogenic | 0.9639 | pathogenic | -2.472 | Highly Destabilizing | 0.999 | D | 0.783 | deleterious | None | None | None | None | N |
| I/D | 0.9978 | likely_pathogenic | 0.998 | pathogenic | -3.783 | Highly Destabilizing | 0.998 | D | 0.88 | deleterious | None | None | None | None | N |
| I/E | 0.9912 | likely_pathogenic | 0.9931 | pathogenic | -3.466 | Highly Destabilizing | 0.998 | D | 0.88 | deleterious | None | None | None | None | N |
| I/F | 0.5143 | ambiguous | 0.5471 | ambiguous | -1.725 | Destabilizing | 0.982 | D | 0.72 | prob.delet. | D | 0.60127743 | None | None | N |
| I/G | 0.9915 | likely_pathogenic | 0.9929 | pathogenic | -3.555 | Highly Destabilizing | 0.998 | D | 0.881 | deleterious | None | None | None | None | N |
| I/H | 0.9784 | likely_pathogenic | 0.9834 | pathogenic | -3.278 | Highly Destabilizing | 0.999 | D | 0.868 | deleterious | None | None | None | None | N |
| I/K | 0.96 | likely_pathogenic | 0.9755 | pathogenic | -2.387 | Highly Destabilizing | 0.993 | D | 0.879 | deleterious | None | None | None | None | N |
| I/L | 0.2214 | likely_benign | 0.2397 | benign | -1.108 | Destabilizing | 0.02 | N | 0.296 | neutral | D | 0.543459508 | None | None | N |
| I/M | 0.2437 | likely_benign | 0.2682 | benign | -1.392 | Destabilizing | 0.982 | D | 0.691 | prob.neutral | D | 0.600873822 | None | None | N |
| I/N | 0.962 | likely_pathogenic | 0.9634 | pathogenic | -3.095 | Highly Destabilizing | 0.997 | D | 0.885 | deleterious | D | 0.611805202 | None | None | N |
| I/P | 0.9961 | likely_pathogenic | 0.9963 | pathogenic | -1.713 | Destabilizing | 0.998 | D | 0.883 | deleterious | None | None | None | None | N |
| I/Q | 0.9732 | likely_pathogenic | 0.9805 | pathogenic | -2.75 | Highly Destabilizing | 0.998 | D | 0.897 | deleterious | None | None | None | None | N |
| I/R | 0.9464 | likely_pathogenic | 0.964 | pathogenic | -2.368 | Highly Destabilizing | 0.993 | D | 0.877 | deleterious | None | None | None | None | N |
| I/S | 0.9642 | likely_pathogenic | 0.9682 | pathogenic | -3.658 | Highly Destabilizing | 0.991 | D | 0.846 | deleterious | D | 0.627824563 | None | None | N |
| I/T | 0.9596 | likely_pathogenic | 0.9677 | pathogenic | -3.181 | Highly Destabilizing | 0.991 | D | 0.772 | deleterious | D | 0.64367248 | None | None | N |
| I/V | 0.1118 | likely_benign | 0.1068 | benign | -1.713 | Destabilizing | 0.58 | D | 0.357 | neutral | D | 0.54850641 | None | None | N |
| I/W | 0.973 | likely_pathogenic | 0.9781 | pathogenic | -2.215 | Highly Destabilizing | 0.999 | D | 0.865 | deleterious | None | None | None | None | N |
| I/Y | 0.9254 | likely_pathogenic | 0.9414 | pathogenic | -2.035 | Highly Destabilizing | 0.998 | D | 0.779 | 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.