Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18964 | 57115;57116;57117 | chr2:178598820;178598819;178598818 | chr2:179463547;179463546;179463545 |
| N2AB | 17323 | 52192;52193;52194 | chr2:178598820;178598819;178598818 | chr2:179463547;179463546;179463545 |
| N2A | 16396 | 49411;49412;49413 | chr2:178598820;178598819;178598818 | chr2:179463547;179463546;179463545 |
| N2B | 9899 | 29920;29921;29922 | chr2:178598820;178598819;178598818 | chr2:179463547;179463546;179463545 |
| Novex-1 | 10024 | 30295;30296;30297 | chr2:178598820;178598819;178598818 | chr2:179463547;179463546;179463545 |
| Novex-2 | 10091 | 30496;30497;30498 | chr2:178598820;178598819;178598818 | chr2:179463547;179463546;179463545 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs770854579  |
-0.934 | 0.993 | N | 0.627 | 0.335 | 0.571034400148 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.54385E-04 | None | 0 | None | 0 | 0 | 0 |
| Y/C | rs770854579 |
-0.934 | 0.993 | N | 0.627 | 0.335 | 0.571034400148 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.9425E-04 | None | 0 | 0 | 0 | 0 | 0 |
| Y/C | rs770854579 |
-0.934 | 0.993 | N | 0.627 | 0.335 | 0.571034400148 | gnomAD-4.0.0 | 2.56372E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.85956E-05 | None | 0 | 0 | 0 | 0 | 0 |
| Y/H | None | None | 0.975 | N | 0.623 | 0.259 | 0.387202362727 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.3662 | ambiguous | 0.3562 | ambiguous | -3.322 | Highly Destabilizing | 0.329 | N | 0.568 | neutral | None | None | None | None | N |
| Y/C | 0.0963 | likely_benign | 0.1079 | benign | -1.628 | Destabilizing | 0.993 | D | 0.627 | neutral | N | 0.439482087 | None | None | N |
| Y/D | 0.6868 | likely_pathogenic | 0.6861 | pathogenic | -3.199 | Highly Destabilizing | 0.642 | D | 0.663 | neutral | N | 0.513670415 | None | None | N |
| Y/E | 0.7986 | likely_pathogenic | 0.8211 | pathogenic | -3.044 | Highly Destabilizing | 0.704 | D | 0.627 | neutral | None | None | None | None | N |
| Y/F | 0.0711 | likely_benign | 0.0806 | benign | -1.346 | Destabilizing | 0.006 | N | 0.285 | neutral | N | 0.393440367 | None | None | N |
| Y/G | 0.5261 | ambiguous | 0.4781 | ambiguous | -3.679 | Highly Destabilizing | 0.543 | D | 0.651 | neutral | None | None | None | None | N |
| Y/H | 0.2099 | likely_benign | 0.2399 | benign | -2.055 | Highly Destabilizing | 0.975 | D | 0.623 | neutral | N | 0.465185822 | None | None | N |
| Y/I | 0.4277 | ambiguous | 0.4688 | ambiguous | -2.14 | Highly Destabilizing | 0.013 | N | 0.335 | neutral | None | None | None | None | N |
| Y/K | 0.7697 | likely_pathogenic | 0.7814 | pathogenic | -2.162 | Highly Destabilizing | 0.704 | D | 0.633 | neutral | None | None | None | None | N |
| Y/L | 0.3499 | ambiguous | 0.3367 | benign | -2.14 | Highly Destabilizing | 0.003 | N | 0.336 | neutral | None | None | None | None | N |
| Y/M | 0.3065 | likely_benign | 0.3536 | ambiguous | -1.656 | Destabilizing | 0.893 | D | 0.618 | neutral | None | None | None | None | N |
| Y/N | 0.244 | likely_benign | 0.248 | benign | -2.719 | Highly Destabilizing | 0.642 | D | 0.645 | neutral | N | 0.484040941 | None | None | N |
| Y/P | 0.9899 | likely_pathogenic | 0.9878 | pathogenic | -2.546 | Highly Destabilizing | 0.944 | D | 0.66 | neutral | None | None | None | None | N |
| Y/Q | 0.5113 | ambiguous | 0.552 | ambiguous | -2.608 | Highly Destabilizing | 0.944 | D | 0.637 | neutral | None | None | None | None | N |
| Y/R | 0.6423 | likely_pathogenic | 0.6465 | pathogenic | -1.66 | Destabilizing | 0.893 | D | 0.633 | neutral | None | None | None | None | N |
| Y/S | 0.1184 | likely_benign | 0.1239 | benign | -3.095 | Highly Destabilizing | 0.01 | N | 0.447 | neutral | N | 0.368312636 | None | None | N |
| Y/T | 0.2397 | likely_benign | 0.2723 | benign | -2.847 | Highly Destabilizing | 0.543 | D | 0.655 | neutral | None | None | None | None | N |
| Y/V | 0.3262 | likely_benign | 0.3568 | ambiguous | -2.546 | Highly Destabilizing | 0.329 | N | 0.533 | neutral | None | None | None | None | N |
| Y/W | 0.4692 | ambiguous | 0.4894 | ambiguous | -0.709 | Destabilizing | 0.981 | D | 0.643 | 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.