Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25710 | 77353;77354;77355 | chr2:178569004;178569003;178569002 | chr2:179433731;179433730;179433729 |
| N2AB | 24069 | 72430;72431;72432 | chr2:178569004;178569003;178569002 | chr2:179433731;179433730;179433729 |
| N2A | 23142 | 69649;69650;69651 | chr2:178569004;178569003;178569002 | chr2:179433731;179433730;179433729 |
| N2B | 16645 | 50158;50159;50160 | chr2:178569004;178569003;178569002 | chr2:179433731;179433730;179433729 |
| Novex-1 | 16770 | 50533;50534;50535 | chr2:178569004;178569003;178569002 | chr2:179433731;179433730;179433729 |
| Novex-2 | 16837 | 50734;50735;50736 | chr2:178569004;178569003;178569002 | chr2:179433731;179433730;179433729 |
| 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/I | rs1250369056  |
-0.672 | 0.47 | N | 0.475 | 0.096 | 0.435043484731 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs1250369056 |
-0.672 | 0.47 | N | 0.475 | 0.096 | 0.435043484731 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 2.62398E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs1250369056 |
-0.672 | 0.47 | N | 0.475 | 0.096 | 0.435043484731 | gnomAD-4.0.0 | 3.7192E-06 | None | None | None | None | N | None | 0 | 8.33834E-05 | None | 0 | 0 | None | 0 | 0 | 8.47772E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7098 | likely_pathogenic | 0.5831 | pathogenic | -1.621 | Destabilizing | 0.585 | D | 0.438 | neutral | N | 0.471625955 | None | None | N |
| V/C | 0.9369 | likely_pathogenic | 0.9142 | pathogenic | -1.964 | Destabilizing | 0.999 | D | 0.664 | neutral | None | None | None | None | N |
| V/D | 0.9757 | likely_pathogenic | 0.9488 | pathogenic | -2.206 | Highly Destabilizing | 0.983 | D | 0.763 | deleterious | N | 0.508594934 | None | None | N |
| V/E | 0.9269 | likely_pathogenic | 0.8714 | pathogenic | -2.16 | Highly Destabilizing | 0.927 | D | 0.623 | neutral | None | None | None | None | N |
| V/F | 0.7238 | likely_pathogenic | 0.6035 | pathogenic | -1.429 | Destabilizing | 0.989 | D | 0.699 | prob.neutral | N | 0.498341492 | None | None | N |
| V/G | 0.8613 | likely_pathogenic | 0.7731 | pathogenic | -1.95 | Destabilizing | 0.919 | D | 0.68 | prob.neutral | N | 0.509608892 | None | None | N |
| V/H | 0.9745 | likely_pathogenic | 0.9541 | pathogenic | -1.504 | Destabilizing | 0.999 | D | 0.742 | deleterious | None | None | None | None | N |
| V/I | 0.0869 | likely_benign | 0.0812 | benign | -0.792 | Destabilizing | 0.47 | N | 0.475 | neutral | N | 0.461588156 | None | None | N |
| V/K | 0.9267 | likely_pathogenic | 0.8629 | pathogenic | -1.365 | Destabilizing | 0.965 | D | 0.634 | neutral | None | None | None | None | N |
| V/L | 0.7242 | likely_pathogenic | 0.6142 | pathogenic | -0.792 | Destabilizing | 0.305 | N | 0.465 | neutral | N | 0.479005788 | None | None | N |
| V/M | 0.4412 | ambiguous | 0.3422 | ambiguous | -0.987 | Destabilizing | 0.996 | D | 0.589 | neutral | None | None | None | None | N |
| V/N | 0.9081 | likely_pathogenic | 0.8466 | pathogenic | -1.451 | Destabilizing | 0.804 | D | 0.772 | deleterious | None | None | None | None | N |
| V/P | 0.9931 | likely_pathogenic | 0.9773 | pathogenic | -1.038 | Destabilizing | 0.893 | D | 0.719 | prob.delet. | None | None | None | None | N |
| V/Q | 0.8921 | likely_pathogenic | 0.8236 | pathogenic | -1.622 | Destabilizing | 0.951 | D | 0.729 | prob.delet. | None | None | None | None | N |
| V/R | 0.906 | likely_pathogenic | 0.8293 | pathogenic | -0.943 | Destabilizing | 0.983 | D | 0.778 | deleterious | None | None | None | None | N |
| V/S | 0.8104 | likely_pathogenic | 0.7231 | pathogenic | -1.99 | Destabilizing | 0.219 | N | 0.347 | neutral | None | None | None | None | N |
| V/T | 0.5457 | ambiguous | 0.475 | ambiguous | -1.827 | Destabilizing | 0.646 | D | 0.413 | neutral | None | None | None | None | N |
| V/W | 0.9915 | likely_pathogenic | 0.984 | pathogenic | -1.636 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| V/Y | 0.9545 | likely_pathogenic | 0.9249 | pathogenic | -1.278 | Destabilizing | 0.997 | D | 0.702 | prob.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.