Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23475 | 70648;70649;70650 | chr2:178575709;178575708;178575707 | chr2:179440436;179440435;179440434 |
| N2AB | 21834 | 65725;65726;65727 | chr2:178575709;178575708;178575707 | chr2:179440436;179440435;179440434 |
| N2A | 20907 | 62944;62945;62946 | chr2:178575709;178575708;178575707 | chr2:179440436;179440435;179440434 |
| N2B | 14410 | 43453;43454;43455 | chr2:178575709;178575708;178575707 | chr2:179440436;179440435;179440434 |
| Novex-1 | 14535 | 43828;43829;43830 | chr2:178575709;178575708;178575707 | chr2:179440436;179440435;179440434 |
| Novex-2 | 14602 | 44029;44030;44031 | chr2:178575709;178575708;178575707 | chr2:179440436;179440435;179440434 |
| 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/C | rs761442543  |
-2.027 | 1.0 | N | 0.754 | 0.471 | 0.612445847935 | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 3.13E-05 | 1.40489E-04 |
| R/C | rs761442543 |
-2.027 | 1.0 | N | 0.754 | 0.471 | 0.612445847935 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| R/C | rs761442543 |
-2.027 | 1.0 | N | 0.754 | 0.471 | 0.612445847935 | gnomAD-4.0.0 | 2.66528E-05 | None | None | None | None | N | None | 0 | 3.33545E-05 | None | 0 | 0 | None | 0 | 0 | 3.39089E-05 | 1.09796E-05 | 0 |
| R/H | rs370257707 |
-2.676 | 0.999 | N | 0.587 | 0.41 | None | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 5.15E-05 | None | 0 | None | 0 | 4.7E-05 | 0 |
| R/H | rs370257707 |
-2.676 | 0.999 | N | 0.587 | 0.41 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.36E-05 | 0 | 0 |
| R/H | rs370257707 |
-2.676 | 0.999 | N | 0.587 | 0.41 | None | gnomAD-4.0.0 | 7.37575E-05 | None | None | None | None | N | None | 1.33526E-05 | 0 | None | 0 | 2.23254E-05 | None | 0 | 0 | 9.40973E-05 | 0 | 9.6083E-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 | 0.993 | likely_pathogenic | 0.9945 | pathogenic | -2.349 | Highly Destabilizing | 0.978 | D | 0.512 | neutral | None | None | None | None | N |
| R/C | 0.8427 | likely_pathogenic | 0.875 | pathogenic | -2.088 | Highly Destabilizing | 1.0 | D | 0.754 | deleterious | N | 0.487501711 | None | None | N |
| R/D | 0.9993 | likely_pathogenic | 0.9993 | pathogenic | -0.839 | Destabilizing | 0.997 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/E | 0.9905 | likely_pathogenic | 0.9913 | pathogenic | -0.633 | Destabilizing | 0.93 | D | 0.439 | neutral | None | None | None | None | N |
| R/F | 0.9957 | likely_pathogenic | 0.9965 | pathogenic | -1.694 | Destabilizing | 0.999 | D | 0.785 | deleterious | None | None | None | None | N |
| R/G | 0.9864 | likely_pathogenic | 0.9884 | pathogenic | -2.671 | Highly Destabilizing | 0.994 | D | 0.643 | neutral | N | 0.509137912 | None | None | N |
| R/H | 0.791 | likely_pathogenic | 0.8154 | pathogenic | -2.383 | Highly Destabilizing | 0.999 | D | 0.587 | neutral | N | 0.502403189 | None | None | N |
| R/I | 0.9932 | likely_pathogenic | 0.9945 | pathogenic | -1.405 | Destabilizing | 0.996 | D | 0.795 | deleterious | None | None | None | None | N |
| R/K | 0.4471 | ambiguous | 0.4655 | ambiguous | -1.41 | Destabilizing | 0.032 | N | 0.224 | neutral | None | None | None | None | N |
| R/L | 0.9772 | likely_pathogenic | 0.9803 | pathogenic | -1.405 | Destabilizing | 0.986 | D | 0.643 | neutral | N | 0.503604503 | None | None | N |
| R/M | 0.9795 | likely_pathogenic | 0.9836 | pathogenic | -1.779 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/N | 0.9975 | likely_pathogenic | 0.9977 | pathogenic | -1.27 | Destabilizing | 0.997 | D | 0.543 | neutral | None | None | None | None | N |
| R/P | 0.9997 | likely_pathogenic | 0.9998 | pathogenic | -1.711 | Destabilizing | 0.999 | D | 0.747 | deleterious | D | 0.545599911 | None | None | N |
| R/Q | 0.7076 | likely_pathogenic | 0.7248 | pathogenic | -1.272 | Destabilizing | 0.996 | D | 0.525 | neutral | None | None | None | None | N |
| R/S | 0.9975 | likely_pathogenic | 0.9981 | pathogenic | -2.345 | Highly Destabilizing | 0.994 | D | 0.603 | neutral | N | 0.488650119 | None | None | N |
| R/T | 0.9955 | likely_pathogenic | 0.9963 | pathogenic | -1.929 | Destabilizing | 0.997 | D | 0.681 | prob.neutral | None | None | None | None | N |
| R/V | 0.9921 | likely_pathogenic | 0.9938 | pathogenic | -1.711 | Destabilizing | 0.989 | D | 0.773 | deleterious | None | None | None | None | N |
| R/W | 0.9485 | likely_pathogenic | 0.9528 | pathogenic | -1.084 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| R/Y | 0.98 | likely_pathogenic | 0.9823 | pathogenic | -0.999 | Destabilizing | 0.999 | D | 0.767 | 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.