Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24595 | 74008;74009;74010 | chr2:178572349;178572348;178572347 | chr2:179437076;179437075;179437074 |
| N2AB | 22954 | 69085;69086;69087 | chr2:178572349;178572348;178572347 | chr2:179437076;179437075;179437074 |
| N2A | 22027 | 66304;66305;66306 | chr2:178572349;178572348;178572347 | chr2:179437076;179437075;179437074 |
| N2B | 15530 | 46813;46814;46815 | chr2:178572349;178572348;178572347 | chr2:179437076;179437075;179437074 |
| Novex-1 | 15655 | 47188;47189;47190 | chr2:178572349;178572348;178572347 | chr2:179437076;179437075;179437074 |
| Novex-2 | 15722 | 47389;47390;47391 | chr2:178572349;178572348;178572347 | chr2:179437076;179437075;179437074 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs543275318  |
-2.015 | 1.0 | D | 0.783 | 0.624 | 0.550047086221 | gnomAD-2.1.1 | 2.57988E-04 | None | None | None | None | N | None | 6.46E-05 | 2.9E-05 | None | 0 | 5.61E-05 | None | 1.86408E-03 | None | 0 | 8.91E-06 | 4.99168E-04 |
| A/T | rs543275318 |
-2.015 | 1.0 | D | 0.783 | 0.624 | 0.550047086221 | gnomAD-3.1.2 | 1.38038E-04 | None | None | None | None | N | None | 4.82E-05 | 7.85855E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 1.24172E-03 | 0 |
| A/T | rs543275318 |
-2.015 | 1.0 | D | 0.783 | 0.624 | 0.550047086221 | gnomAD-4.0.0 | 1.24085E-04 | None | None | None | None | N | None | 4.00652E-05 | 2.50192E-04 | None | 0 | 2.23684E-05 | None | 0 | 3.29598E-04 | 6.78933E-06 | 1.84514E-03 | 4.81031E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.9264 | likely_pathogenic | 0.8679 | pathogenic | -2.002 | Highly Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| A/D | 0.9993 | likely_pathogenic | 0.9983 | pathogenic | -3.006 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| A/E | 0.9984 | likely_pathogenic | 0.9965 | pathogenic | -2.768 | Highly Destabilizing | 1.0 | D | 0.862 | deleterious | D | 0.579055349 | None | None | N |
| A/F | 0.9978 | likely_pathogenic | 0.9943 | pathogenic | -0.86 | Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| A/G | 0.3448 | ambiguous | 0.2778 | benign | -2.404 | Highly Destabilizing | 1.0 | D | 0.615 | neutral | N | 0.520436944 | None | None | N |
| A/H | 0.9992 | likely_pathogenic | 0.9982 | pathogenic | -2.183 | Highly Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| A/I | 0.9964 | likely_pathogenic | 0.9877 | pathogenic | -0.762 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| A/K | 0.9997 | likely_pathogenic | 0.9993 | pathogenic | -1.556 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| A/L | 0.9677 | likely_pathogenic | 0.9372 | pathogenic | -0.762 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| A/M | 0.9911 | likely_pathogenic | 0.9776 | pathogenic | -1.348 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| A/N | 0.9979 | likely_pathogenic | 0.9952 | pathogenic | -2.062 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| A/P | 0.7957 | likely_pathogenic | 0.5622 | ambiguous | -1.136 | Destabilizing | 1.0 | D | 0.869 | deleterious | D | 0.523185648 | None | None | N |
| A/Q | 0.9964 | likely_pathogenic | 0.9929 | pathogenic | -1.782 | Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | N |
| A/R | 0.9979 | likely_pathogenic | 0.9958 | pathogenic | -1.627 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| A/S | 0.5711 | likely_pathogenic | 0.4711 | ambiguous | -2.417 | Highly Destabilizing | 1.0 | D | 0.597 | neutral | N | 0.516598602 | None | None | N |
| A/T | 0.9616 | likely_pathogenic | 0.9121 | pathogenic | -2.068 | Highly Destabilizing | 1.0 | D | 0.783 | deleterious | D | 0.552375812 | None | None | N |
| A/V | 0.9733 | likely_pathogenic | 0.9231 | pathogenic | -1.136 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | D | 0.558923178 | None | None | N |
| A/W | 0.9997 | likely_pathogenic | 0.9991 | pathogenic | -1.416 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| A/Y | 0.999 | likely_pathogenic | 0.9975 | pathogenic | -1.165 | Destabilizing | 1.0 | D | 0.909 | 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.