Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21799 | 65620;65621;65622 | chr2:178583787;178583786;178583785 | chr2:179448514;179448513;179448512 |
| N2AB | 20158 | 60697;60698;60699 | chr2:178583787;178583786;178583785 | chr2:179448514;179448513;179448512 |
| N2A | 19231 | 57916;57917;57918 | chr2:178583787;178583786;178583785 | chr2:179448514;179448513;179448512 |
| N2B | 12734 | 38425;38426;38427 | chr2:178583787;178583786;178583785 | chr2:179448514;179448513;179448512 |
| Novex-1 | 12859 | 38800;38801;38802 | chr2:178583787;178583786;178583785 | chr2:179448514;179448513;179448512 |
| Novex-2 | 12926 | 39001;39002;39003 | chr2:178583787;178583786;178583785 | chr2:179448514;179448513;179448512 |
| 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/P | rs1260259069  |
-1.145 | 0.235 | N | 0.554 | 0.333 | 0.685930098433 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.35E-05 | None | 0 | 0 | 0 |
| L/P | rs1260259069 |
-1.145 | 0.235 | N | 0.554 | 0.333 | 0.685930098433 | gnomAD-4.0.0 | 1.59838E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.44371E-05 | 0 |
| L/R | None | None | 0.997 | N | 0.741 | 0.43 | 0.771267463846 | gnomAD-4.0.0 | 3.19676E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.88742E-05 | 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 | 0.5098 | ambiguous | 0.3959 | ambiguous | -1.68 | Destabilizing | 0.983 | D | 0.47 | neutral | None | None | None | None | N |
| L/C | 0.7188 | likely_pathogenic | 0.6209 | pathogenic | -0.769 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | N |
| L/D | 0.8664 | likely_pathogenic | 0.8006 | pathogenic | -1.014 | Destabilizing | 0.998 | D | 0.742 | deleterious | None | None | None | None | N |
| L/E | 0.5867 | likely_pathogenic | 0.4688 | ambiguous | -0.999 | Destabilizing | 0.995 | D | 0.723 | prob.delet. | None | None | None | None | N |
| L/F | 0.3094 | likely_benign | 0.225 | benign | -1.14 | Destabilizing | 0.999 | D | 0.663 | neutral | N | 0.479055014 | None | None | N |
| L/G | 0.7279 | likely_pathogenic | 0.6524 | pathogenic | -2.012 | Highly Destabilizing | 0.995 | D | 0.729 | prob.delet. | None | None | None | None | N |
| L/H | 0.4692 | ambiguous | 0.3477 | ambiguous | -1.135 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | N | 0.515441284 | None | None | N |
| L/I | 0.0981 | likely_benign | 0.0809 | benign | -0.831 | Destabilizing | 0.989 | D | 0.439 | neutral | N | 0.496335448 | None | None | N |
| L/K | 0.4485 | ambiguous | 0.3368 | benign | -1.049 | Destabilizing | 0.995 | D | 0.721 | prob.delet. | None | None | None | None | N |
| L/M | 0.1685 | likely_benign | 0.1355 | benign | -0.566 | Destabilizing | 0.999 | D | 0.652 | neutral | None | None | None | None | N |
| L/N | 0.544 | ambiguous | 0.463 | ambiguous | -0.83 | Destabilizing | 0.998 | D | 0.742 | deleterious | None | None | None | None | N |
| L/P | 0.736 | likely_pathogenic | 0.6618 | pathogenic | -1.084 | Destabilizing | 0.235 | N | 0.554 | neutral | N | 0.442098318 | None | None | N |
| L/Q | 0.2925 | likely_benign | 0.2072 | benign | -0.998 | Destabilizing | 0.998 | D | 0.738 | prob.delet. | None | None | None | None | N |
| L/R | 0.4226 | ambiguous | 0.3041 | benign | -0.437 | Destabilizing | 0.997 | D | 0.741 | deleterious | N | 0.503069419 | None | None | N |
| L/S | 0.5774 | likely_pathogenic | 0.461 | ambiguous | -1.452 | Destabilizing | 0.995 | D | 0.727 | prob.delet. | None | None | None | None | N |
| L/T | 0.4374 | ambiguous | 0.3422 | ambiguous | -1.321 | Destabilizing | 0.995 | D | 0.56 | neutral | None | None | None | None | N |
| L/V | 0.1278 | likely_benign | 0.1018 | benign | -1.084 | Destabilizing | 0.989 | D | 0.475 | neutral | N | 0.427166151 | None | None | N |
| L/W | 0.4821 | ambiguous | 0.3726 | ambiguous | -1.217 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| L/Y | 0.5019 | ambiguous | 0.3931 | ambiguous | -1.004 | Destabilizing | 0.999 | D | 0.674 | neutral | 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.