Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32727 | 98404;98405;98406 | chr2:178539886;178539885;178539884 | chr2:179404613;179404612;179404611 |
| N2AB | 31086 | 93481;93482;93483 | chr2:178539886;178539885;178539884 | chr2:179404613;179404612;179404611 |
| N2A | 30159 | 90700;90701;90702 | chr2:178539886;178539885;178539884 | chr2:179404613;179404612;179404611 |
| N2B | 23662 | 71209;71210;71211 | chr2:178539886;178539885;178539884 | chr2:179404613;179404612;179404611 |
| Novex-1 | 23787 | 71584;71585;71586 | chr2:178539886;178539885;178539884 | chr2:179404613;179404612;179404611 |
| Novex-2 | 23854 | 71785;71786;71787 | chr2:178539886;178539885;178539884 | chr2:179404613;179404612;179404611 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | None | None | 1.0 | N | 0.745 | 0.386 | 0.501559347837 | gnomAD-4.0.0 | 6.84203E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99476E-07 | 0 | 0 |
| P/T | rs1276534291  |
-0.253 | 1.0 | N | 0.737 | 0.409 | 0.512192450023 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| P/T | rs1276534291 |
-0.253 | 1.0 | N | 0.737 | 0.409 | 0.512192450023 | gnomAD-4.0.0 | 6.84203E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99476E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.2042 | likely_benign | 0.2174 | benign | -0.841 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | N | 0.481120426 | None | None | I |
| P/C | 0.8022 | likely_pathogenic | 0.8188 | pathogenic | -0.68 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | I |
| P/D | 0.7435 | likely_pathogenic | 0.7569 | pathogenic | -0.787 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| P/E | 0.6635 | likely_pathogenic | 0.6711 | pathogenic | -0.859 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| P/F | 0.8125 | likely_pathogenic | 0.8349 | pathogenic | -0.822 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| P/G | 0.5566 | ambiguous | 0.5421 | ambiguous | -1.041 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| P/H | 0.5077 | ambiguous | 0.535 | ambiguous | -0.549 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | I |
| P/I | 0.7275 | likely_pathogenic | 0.7373 | pathogenic | -0.435 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | I |
| P/K | 0.6394 | likely_pathogenic | 0.659 | pathogenic | -0.841 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| P/L | 0.3471 | ambiguous | 0.3741 | ambiguous | -0.435 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.492680996 | None | None | I |
| P/M | 0.7015 | likely_pathogenic | 0.7134 | pathogenic | -0.443 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | I |
| P/N | 0.6302 | likely_pathogenic | 0.6374 | pathogenic | -0.61 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| P/Q | 0.4629 | ambiguous | 0.4789 | ambiguous | -0.829 | Destabilizing | 1.0 | D | 0.74 | deleterious | D | 0.53363276 | None | None | I |
| P/R | 0.4691 | ambiguous | 0.4912 | ambiguous | -0.265 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | N | 0.515297716 | None | None | I |
| P/S | 0.3125 | likely_benign | 0.3197 | benign | -0.965 | Destabilizing | 1.0 | D | 0.745 | deleterious | N | 0.517721945 | None | None | I |
| P/T | 0.3321 | likely_benign | 0.3377 | benign | -0.936 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.518412592 | None | None | I |
| P/V | 0.575 | likely_pathogenic | 0.5775 | pathogenic | -0.535 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| P/W | 0.8924 | likely_pathogenic | 0.913 | pathogenic | -0.949 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | I |
| P/Y | 0.8009 | likely_pathogenic | 0.8161 | pathogenic | -0.666 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
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.