Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30231 | 90916;90917;90918 | chr2:178552209;178552208;178552207 | chr2:179416936;179416935;179416934 |
| N2AB | 28590 | 85993;85994;85995 | chr2:178552209;178552208;178552207 | chr2:179416936;179416935;179416934 |
| N2A | 27663 | 83212;83213;83214 | chr2:178552209;178552208;178552207 | chr2:179416936;179416935;179416934 |
| N2B | 21166 | 63721;63722;63723 | chr2:178552209;178552208;178552207 | chr2:179416936;179416935;179416934 |
| Novex-1 | 21291 | 64096;64097;64098 | chr2:178552209;178552208;178552207 | chr2:179416936;179416935;179416934 |
| Novex-2 | 21358 | 64297;64298;64299 | chr2:178552209;178552208;178552207 | chr2:179416936;179416935;179416934 |
| 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 | rs373722546  |
-0.976 | 1.0 | D | 0.858 | 0.466 | None | gnomAD-2.1.1 | 4.65E-05 | None | None | None | None | I | None | 5.37545E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs373722546 |
-0.976 | 1.0 | D | 0.858 | 0.466 | None | gnomAD-3.1.2 | 1.31475E-04 | None | None | None | None | I | None | 4.82649E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs373722546 |
-0.976 | 1.0 | D | 0.858 | 0.466 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | I | None | 2.3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| P/S | rs373722546 |
-0.976 | 1.0 | D | 0.858 | 0.466 | None | gnomAD-4.0.0 | 1.79737E-05 | None | None | None | None | I | None | 3.73194E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60123E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.2897 | likely_benign | 0.2868 | benign | -0.548 | Destabilizing | 1.0 | D | 0.771 | deleterious | D | 0.529404533 | None | None | I |
| P/C | 0.7781 | likely_pathogenic | 0.7856 | pathogenic | -0.72 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | I |
| P/D | 0.6573 | likely_pathogenic | 0.6787 | pathogenic | -0.281 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | I |
| P/E | 0.5309 | ambiguous | 0.5477 | ambiguous | -0.369 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | I |
| P/F | 0.8193 | likely_pathogenic | 0.8317 | pathogenic | -0.587 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | I |
| P/G | 0.6726 | likely_pathogenic | 0.6724 | pathogenic | -0.714 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | I |
| P/H | 0.5115 | ambiguous | 0.528 | ambiguous | -0.177 | Destabilizing | 1.0 | D | 0.83 | deleterious | D | 0.542028286 | None | None | I |
| P/I | 0.6192 | likely_pathogenic | 0.6603 | pathogenic | -0.249 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | I |
| P/K | 0.6227 | likely_pathogenic | 0.643 | pathogenic | -0.548 | Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | I |
| P/L | 0.3705 | ambiguous | 0.3889 | ambiguous | -0.249 | Destabilizing | 1.0 | D | 0.873 | deleterious | N | 0.512217968 | None | None | I |
| P/M | 0.5935 | likely_pathogenic | 0.6251 | pathogenic | -0.428 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | I |
| P/N | 0.5844 | likely_pathogenic | 0.6093 | pathogenic | -0.32 | Destabilizing | 1.0 | D | 0.898 | deleterious | None | None | None | None | I |
| P/Q | 0.4314 | ambiguous | 0.4497 | ambiguous | -0.529 | Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | I |
| P/R | 0.5214 | ambiguous | 0.5253 | ambiguous | -0.032 | Destabilizing | 1.0 | D | 0.896 | deleterious | N | 0.515023261 | None | None | I |
| P/S | 0.4359 | ambiguous | 0.4411 | ambiguous | -0.72 | Destabilizing | 1.0 | D | 0.858 | deleterious | D | 0.523328146 | None | None | I |
| P/T | 0.3253 | likely_benign | 0.3448 | ambiguous | -0.702 | Destabilizing | 1.0 | D | 0.858 | deleterious | N | 0.505223891 | None | None | I |
| P/V | 0.4908 | ambiguous | 0.5189 | ambiguous | -0.313 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | I |
| P/W | 0.9293 | likely_pathogenic | 0.93 | pathogenic | -0.669 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | I |
| P/Y | 0.8011 | likely_pathogenic | 0.8085 | pathogenic | -0.385 | Destabilizing | 1.0 | D | 0.864 | deleterious | 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.