Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23277 | 70054;70055;70056 | chr2:178576303;178576302;178576301 | chr2:179441030;179441029;179441028 |
| N2AB | 21636 | 65131;65132;65133 | chr2:178576303;178576302;178576301 | chr2:179441030;179441029;179441028 |
| N2A | 20709 | 62350;62351;62352 | chr2:178576303;178576302;178576301 | chr2:179441030;179441029;179441028 |
| N2B | 14212 | 42859;42860;42861 | chr2:178576303;178576302;178576301 | chr2:179441030;179441029;179441028 |
| Novex-1 | 14337 | 43234;43235;43236 | chr2:178576303;178576302;178576301 | chr2:179441030;179441029;179441028 |
| Novex-2 | 14404 | 43435;43436;43437 | chr2:178576303;178576302;178576301 | chr2:179441030;179441029;179441028 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/M | rs371513781  |
-0.551 | 1.0 | N | 0.775 | 0.423 | None | gnomAD-2.1.1 | 7.61E-05 | None | None | None | None | N | None | 4.25E-05 | 0 | None | 0 | 5.5E-05 | None | 5.48477E-04 | None | 4.26E-05 | 2.58E-05 | 0 |
| V/M | rs371513781 |
-0.551 | 1.0 | N | 0.775 | 0.423 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 4.41E-05 | 0 | 0 |
| V/M | rs371513781 |
-0.551 | 1.0 | N | 0.775 | 0.423 | None | gnomAD-4.0.0 | 4.04569E-05 | None | None | None | None | N | None | 1.36545E-05 | 0 | None | 0 | 2.24568E-05 | None | 1.59826E-05 | 0 | 2.14128E-05 | 4.13096E-04 | 1.63838E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7688 | likely_pathogenic | 0.7301 | pathogenic | -2.333 | Highly Destabilizing | 0.998 | D | 0.66 | neutral | D | 0.545591863 | None | None | N |
| V/C | 0.9718 | likely_pathogenic | 0.97 | pathogenic | -1.726 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| V/D | 0.9983 | likely_pathogenic | 0.9983 | pathogenic | -3.337 | Highly Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| V/E | 0.9934 | likely_pathogenic | 0.9934 | pathogenic | -3.0 | Highly Destabilizing | 1.0 | D | 0.849 | deleterious | D | 0.546352332 | None | None | N |
| V/F | 0.8937 | likely_pathogenic | 0.8917 | pathogenic | -1.339 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| V/G | 0.9439 | likely_pathogenic | 0.9388 | pathogenic | -2.956 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | D | 0.546352332 | None | None | N |
| V/H | 0.9982 | likely_pathogenic | 0.9982 | pathogenic | -2.934 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| V/I | 0.0942 | likely_benign | 0.0964 | benign | -0.502 | Destabilizing | 0.813 | D | 0.312 | neutral | None | None | None | None | N |
| V/K | 0.9943 | likely_pathogenic | 0.9942 | pathogenic | -1.882 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| V/L | 0.5151 | ambiguous | 0.5052 | ambiguous | -0.502 | Destabilizing | 0.992 | D | 0.629 | neutral | N | 0.51848995 | None | None | N |
| V/M | 0.6862 | likely_pathogenic | 0.6734 | pathogenic | -0.8 | Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.516384792 | None | None | N |
| V/N | 0.995 | likely_pathogenic | 0.9952 | pathogenic | -2.641 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| V/P | 0.9902 | likely_pathogenic | 0.9896 | pathogenic | -1.096 | Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | N |
| V/Q | 0.9919 | likely_pathogenic | 0.9921 | pathogenic | -2.23 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| V/R | 0.9872 | likely_pathogenic | 0.987 | pathogenic | -2.097 | Highly Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | N |
| V/S | 0.9689 | likely_pathogenic | 0.9665 | pathogenic | -3.115 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| V/T | 0.8361 | likely_pathogenic | 0.8269 | pathogenic | -2.609 | Highly Destabilizing | 0.998 | D | 0.701 | prob.neutral | None | None | None | None | N |
| V/W | 0.998 | likely_pathogenic | 0.9978 | pathogenic | -1.897 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| V/Y | 0.9937 | likely_pathogenic | 0.9934 | pathogenic | -1.592 | Destabilizing | 1.0 | D | 0.807 | 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.