Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6703 | 20332;20333;20334 | chr2:178727258;178727257;178727256 | chr2:179591985;179591984;179591983 |
| N2AB | 6386 | 19381;19382;19383 | chr2:178727258;178727257;178727256 | chr2:179591985;179591984;179591983 |
| N2A | 5459 | 16600;16601;16602 | chr2:178727258;178727257;178727256 | chr2:179591985;179591984;179591983 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | None | None | 0.549 | N | 0.566 | 0.2 | 0.275641507738 | gnomAD-4.0.0 | 6.84488E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99748E-07 | 0 | 0 |
| R/Q | rs546821182  |
-0.982 | 0.574 | N | 0.487 | 0.18 | None | gnomAD-2.1.1 | 4.65E-05 | None | None | None | None | N | None | 2.48324E-04 | 2.84E-05 | None | 0 | 1.02775E-04 | None | 0 | None | 0 | 2.35E-05 | 1.40845E-04 |
| R/Q | rs546821182 |
-0.982 | 0.574 | N | 0.487 | 0.18 | None | gnomAD-3.1.2 | 1.44689E-04 | None | None | None | None | N | None | 3.13813E-04 | 3.27912E-04 | 0 | 0 | 1.93573E-04 | None | 0 | 6.32911E-03 | 1.47E-05 | 0 | 0 |
| R/Q | rs546821182 |
-0.982 | 0.574 | N | 0.487 | 0.18 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs546821182 |
-0.982 | 0.574 | N | 0.487 | 0.18 | None | gnomAD-4.0.0 | 3.40956E-05 | None | None | None | None | N | None | 2.93412E-04 | 1.16799E-04 | None | 0 | 4.46449E-05 | None | 0 | 9.9108E-04 | 1.18704E-05 | 1.09844E-05 | 4.80569E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5287 | ambiguous | 0.6064 | pathogenic | -1.765 | Destabilizing | 0.116 | N | 0.493 | neutral | None | None | None | None | N |
| R/C | 0.2235 | likely_benign | 0.2001 | benign | -1.621 | Destabilizing | 0.981 | D | 0.649 | neutral | None | None | None | None | N |
| R/D | 0.8737 | likely_pathogenic | 0.8976 | pathogenic | -0.566 | Destabilizing | 0.241 | N | 0.562 | neutral | None | None | None | None | N |
| R/E | 0.4914 | ambiguous | 0.5487 | ambiguous | -0.37 | Destabilizing | 0.002 | N | 0.167 | neutral | None | None | None | None | N |
| R/F | 0.6539 | likely_pathogenic | 0.7017 | pathogenic | -1.303 | Destabilizing | 0.932 | D | 0.633 | neutral | None | None | None | None | N |
| R/G | 0.4435 | ambiguous | 0.5318 | ambiguous | -2.133 | Highly Destabilizing | 0.549 | D | 0.563 | neutral | N | 0.466393764 | None | None | N |
| R/H | 0.125 | likely_benign | 0.1287 | benign | -2.233 | Highly Destabilizing | 0.818 | D | 0.541 | neutral | None | None | None | None | N |
| R/I | 0.3207 | likely_benign | 0.3513 | ambiguous | -0.721 | Destabilizing | 0.818 | D | 0.628 | neutral | None | None | None | None | N |
| R/K | 0.0898 | likely_benign | 0.095 | benign | -1.267 | Destabilizing | None | N | 0.112 | neutral | None | None | None | None | N |
| R/L | 0.2754 | likely_benign | 0.3146 | benign | -0.721 | Destabilizing | 0.549 | D | 0.566 | neutral | N | 0.456452583 | None | None | N |
| R/M | 0.3389 | likely_benign | 0.3982 | ambiguous | -1.004 | Destabilizing | 0.932 | D | 0.606 | neutral | None | None | None | None | N |
| R/N | 0.7311 | likely_pathogenic | 0.7852 | pathogenic | -1.057 | Destabilizing | 0.388 | N | 0.463 | neutral | None | None | None | None | N |
| R/P | 0.9443 | likely_pathogenic | 0.9562 | pathogenic | -1.054 | Destabilizing | 0.896 | D | 0.627 | neutral | N | 0.49874116 | None | None | N |
| R/Q | 0.0995 | likely_benign | 0.1035 | benign | -1.082 | Destabilizing | 0.574 | D | 0.487 | neutral | N | 0.463747191 | None | None | N |
| R/S | 0.6022 | likely_pathogenic | 0.6689 | pathogenic | -2.045 | Highly Destabilizing | 0.241 | N | 0.535 | neutral | None | None | None | None | N |
| R/T | 0.4227 | ambiguous | 0.5077 | ambiguous | -1.617 | Destabilizing | 0.388 | N | 0.516 | neutral | None | None | None | None | N |
| R/V | 0.4456 | ambiguous | 0.4671 | ambiguous | -1.054 | Destabilizing | 0.388 | N | 0.617 | neutral | None | None | None | None | N |
| R/W | 0.2124 | likely_benign | 0.2278 | benign | -0.779 | Destabilizing | 0.981 | D | 0.668 | neutral | None | None | None | None | N |
| R/Y | 0.4725 | ambiguous | 0.5051 | ambiguous | -0.609 | Destabilizing | 0.932 | D | 0.627 | 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.