Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15772 | 47539;47540;47541 | chr2:178618037;178618036;178618035 | chr2:179482764;179482763;179482762 |
| N2AB | 14131 | 42616;42617;42618 | chr2:178618037;178618036;178618035 | chr2:179482764;179482763;179482762 |
| N2A | 13204 | 39835;39836;39837 | chr2:178618037;178618036;178618035 | chr2:179482764;179482763;179482762 |
| N2B | 6707 | 20344;20345;20346 | chr2:178618037;178618036;178618035 | chr2:179482764;179482763;179482762 |
| Novex-1 | 6832 | 20719;20720;20721 | chr2:178618037;178618036;178618035 | chr2:179482764;179482763;179482762 |
| Novex-2 | 6899 | 20920;20921;20922 | chr2:178618037;178618036;178618035 | chr2:179482764;179482763;179482762 |
| 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 | D | 0.453 | 0.252 | 0.393927044628 | gnomAD-4.0.0 | 6.84747E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99928E-07 | 0 | 0 |
| R/Q | rs72677233  |
-0.714 | 0.574 | N | 0.469 | 0.113 | None | gnomAD-2.1.1 | 3.18798E-03 | None | None | None | None | N | None | 5.79278E-04 | 1.76106E-03 | None | 3.16137E-02 | 0 | None | 1.76494E-03 | None | 3.20128E-04 | 3.07231E-03 | 4.79413E-03 |
| R/Q | rs72677233 |
-0.714 | 0.574 | N | 0.469 | 0.113 | None | gnomAD-3.1.2 | 2.91682E-03 | None | None | None | None | N | None | 3.3823E-04 | 6.50545E-03 | 0 | 2.68166E-02 | 0 | None | 2.82486E-04 | 9.49367E-03 | 2.94594E-03 | 2.48344E-03 | 9.09962E-03 |
| R/Q | rs72677233 |
-0.714 | 0.574 | N | 0.469 | 0.113 | None | 1000 genomes | 1.39776E-03 | None | None | None | None | N | None | 0 | 4.3E-03 | None | None | 0 | 2E-03 | None | None | None | 2E-03 | None |
| R/Q | rs72677233 |
-0.714 | 0.574 | N | 0.469 | 0.113 | None | gnomAD-4.0.0 | 2.77848E-03 | None | None | None | None | N | None | 6.54118E-04 | 3.09055E-03 | None | 3.29905E-02 | 2.24215E-05 | None | 2.65642E-04 | 1.22355E-02 | 2.28992E-03 | 1.85629E-03 | 4.96906E-03 |
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 | 0.5948 | likely_pathogenic | 0.5936 | pathogenic | -0.276 | Destabilizing | 0.116 | N | 0.409 | neutral | None | None | None | None | N |
| R/C | 0.3416 | ambiguous | 0.3261 | benign | -0.301 | Destabilizing | 0.981 | D | 0.543 | neutral | None | None | None | None | N |
| R/D | 0.8466 | likely_pathogenic | 0.8598 | pathogenic | -0.058 | Destabilizing | 0.388 | N | 0.463 | neutral | None | None | None | None | N |
| R/E | 0.6071 | likely_pathogenic | 0.6007 | pathogenic | 0.047 | Stabilizing | 0.116 | N | 0.409 | neutral | None | None | None | None | N |
| R/F | 0.8632 | likely_pathogenic | 0.8797 | pathogenic | -0.303 | Destabilizing | 0.932 | D | 0.525 | neutral | None | None | None | None | N |
| R/G | 0.4245 | ambiguous | 0.4569 | ambiguous | -0.542 | Destabilizing | 0.549 | D | 0.453 | neutral | N | 0.469062239 | None | None | N |
| R/H | 0.2088 | likely_benign | 0.2067 | benign | -1.14 | Destabilizing | 0.818 | D | 0.384 | neutral | None | None | None | None | N |
| R/I | 0.5614 | ambiguous | 0.5703 | pathogenic | 0.411 | Stabilizing | 0.818 | D | 0.534 | neutral | None | None | None | None | N |
| R/K | 0.1412 | likely_benign | 0.1334 | benign | -0.315 | Destabilizing | None | N | 0.091 | neutral | None | None | None | None | N |
| R/L | 0.4735 | ambiguous | 0.5008 | ambiguous | 0.411 | Stabilizing | 0.549 | D | 0.453 | neutral | D | 0.565441199 | None | None | N |
| R/M | 0.5714 | likely_pathogenic | 0.5783 | pathogenic | -0.047 | Destabilizing | 0.932 | D | 0.418 | neutral | None | None | None | None | N |
| R/N | 0.7238 | likely_pathogenic | 0.7482 | pathogenic | 0.015 | Stabilizing | 0.388 | N | 0.415 | neutral | None | None | None | None | N |
| R/P | 0.6847 | likely_pathogenic | 0.7207 | pathogenic | 0.204 | Stabilizing | 0.896 | D | 0.471 | neutral | N | 0.473838112 | None | None | N |
| R/Q | 0.1796 | likely_benign | 0.1706 | benign | -0.07 | Destabilizing | 0.574 | D | 0.469 | neutral | N | 0.475720943 | None | None | N |
| R/S | 0.6251 | likely_pathogenic | 0.658 | pathogenic | -0.471 | Destabilizing | 0.241 | N | 0.433 | neutral | None | None | None | None | N |
| R/T | 0.4998 | ambiguous | 0.5122 | ambiguous | -0.198 | Destabilizing | 0.388 | N | 0.445 | neutral | None | None | None | None | N |
| R/V | 0.6499 | likely_pathogenic | 0.6587 | pathogenic | 0.204 | Stabilizing | 0.69 | D | 0.484 | neutral | None | None | None | None | N |
| R/W | 0.5495 | ambiguous | 0.5747 | pathogenic | -0.207 | Destabilizing | 0.981 | D | 0.643 | neutral | None | None | None | None | N |
| R/Y | 0.6834 | likely_pathogenic | 0.7102 | pathogenic | 0.157 | Stabilizing | 0.932 | D | 0.503 | 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.