Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21125 | 63598;63599;63600 | chr2:178588034;178588033;178588032 | chr2:179452761;179452760;179452759 |
| N2AB | 19484 | 58675;58676;58677 | chr2:178588034;178588033;178588032 | chr2:179452761;179452760;179452759 |
| N2A | 18557 | 55894;55895;55896 | chr2:178588034;178588033;178588032 | chr2:179452761;179452760;179452759 |
| N2B | 12060 | 36403;36404;36405 | chr2:178588034;178588033;178588032 | chr2:179452761;179452760;179452759 |
| Novex-1 | 12185 | 36778;36779;36780 | chr2:178588034;178588033;178588032 | chr2:179452761;179452760;179452759 |
| Novex-2 | 12252 | 36979;36980;36981 | chr2:178588034;178588033;178588032 | chr2:179452761;179452760;179452759 |
| 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 | rs1040226223  |
-1.78 | 0.993 | N | 0.787 | 0.257 | 0.40017627803 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66223E-04 |
| L/F | rs1040226223 |
-1.78 | 0.993 | N | 0.787 | 0.257 | 0.40017627803 | gnomAD-4.0.0 | 1.59301E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.027E-05 |
| L/I | None | None | 0.955 | N | 0.545 | 0.18 | 0.31077124679 | gnomAD-4.0.0 | 1.59301E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.4334E-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 | 0.4433 | ambiguous | 0.4864 | ambiguous | -2.072 | Highly Destabilizing | 0.966 | D | 0.552 | neutral | None | None | None | None | N |
| L/C | 0.6759 | likely_pathogenic | 0.7201 | pathogenic | -1.215 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| L/D | 0.8809 | likely_pathogenic | 0.8986 | pathogenic | -2.049 | Highly Destabilizing | 0.999 | D | 0.813 | deleterious | None | None | None | None | N |
| L/E | 0.683 | likely_pathogenic | 0.7028 | pathogenic | -1.809 | Destabilizing | 0.998 | D | 0.779 | deleterious | None | None | None | None | N |
| L/F | 0.3639 | ambiguous | 0.3956 | ambiguous | -1.145 | Destabilizing | 0.993 | D | 0.787 | deleterious | N | 0.452196167 | None | None | N |
| L/G | 0.7378 | likely_pathogenic | 0.774 | pathogenic | -2.625 | Highly Destabilizing | 0.998 | D | 0.772 | deleterious | None | None | None | None | N |
| L/H | 0.5971 | likely_pathogenic | 0.6465 | pathogenic | -2.101 | Highly Destabilizing | 1.0 | D | 0.821 | deleterious | N | 0.463970546 | None | None | N |
| L/I | 0.1079 | likely_benign | 0.1225 | benign | -0.484 | Destabilizing | 0.955 | D | 0.545 | neutral | N | 0.442449743 | None | None | N |
| L/K | 0.6757 | likely_pathogenic | 0.6981 | pathogenic | -1.362 | Destabilizing | 0.998 | D | 0.719 | prob.delet. | None | None | None | None | N |
| L/M | 0.1831 | likely_benign | 0.1879 | benign | -0.453 | Destabilizing | 0.998 | D | 0.779 | deleterious | None | None | None | None | N |
| L/N | 0.6227 | likely_pathogenic | 0.6451 | pathogenic | -1.708 | Destabilizing | 0.999 | D | 0.814 | deleterious | None | None | None | None | N |
| L/P | 0.6525 | likely_pathogenic | 0.6715 | pathogenic | -0.993 | Destabilizing | 0.999 | D | 0.807 | deleterious | N | 0.453493456 | None | None | N |
| L/Q | 0.4977 | ambiguous | 0.5206 | ambiguous | -1.524 | Destabilizing | 0.999 | D | 0.798 | deleterious | None | None | None | None | N |
| L/R | 0.5962 | likely_pathogenic | 0.63 | pathogenic | -1.242 | Destabilizing | 0.997 | D | 0.785 | deleterious | N | 0.463210078 | None | None | N |
| L/S | 0.6515 | likely_pathogenic | 0.6886 | pathogenic | -2.436 | Highly Destabilizing | 0.998 | D | 0.717 | prob.delet. | None | None | None | None | N |
| L/T | 0.3833 | ambiguous | 0.4035 | ambiguous | -2.042 | Highly Destabilizing | 0.995 | D | 0.719 | prob.delet. | None | None | None | None | N |
| L/V | 0.1022 | likely_benign | 0.1169 | benign | -0.993 | Destabilizing | 0.117 | N | 0.434 | neutral | N | 0.422189114 | None | None | N |
| L/W | 0.5593 | ambiguous | 0.6285 | pathogenic | -1.522 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| L/Y | 0.6467 | likely_pathogenic | 0.6853 | pathogenic | -1.164 | Destabilizing | 0.998 | D | 0.774 | 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.