Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15327 | 46204;46205;46206 | chr2:178620542;178620541;178620540 | chr2:179485269;179485268;179485267 |
| N2AB | 13686 | 41281;41282;41283 | chr2:178620542;178620541;178620540 | chr2:179485269;179485268;179485267 |
| N2A | 12759 | 38500;38501;38502 | chr2:178620542;178620541;178620540 | chr2:179485269;179485268;179485267 |
| N2B | 6262 | 19009;19010;19011 | chr2:178620542;178620541;178620540 | chr2:179485269;179485268;179485267 |
| Novex-1 | 6387 | 19384;19385;19386 | chr2:178620542;178620541;178620540 | chr2:179485269;179485268;179485267 |
| Novex-2 | 6454 | 19585;19586;19587 | chr2:178620542;178620541;178620540 | chr2:179485269;179485268;179485267 |
| 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 | rs367774903  |
-0.132 | 1.0 | D | 0.591 | 0.468 | None | gnomAD-2.1.1 | 1.68987E-04 | None | None | None | None | N | None | 0 | 0 | None | 9.74E-05 | 0 | None | 3.29E-05 | None | 2.40751E-04 | 2.99293E-04 | 1.41804E-04 |
| R/C | rs367774903 |
-0.132 | 1.0 | D | 0.591 | 0.468 | None | gnomAD-3.1.2 | 1.44834E-04 | None | None | None | None | N | None | 0 | 6.57E-05 | 0 | 0 | 0 | None | 2.82859E-04 | 0 | 2.65127E-04 | 0 | 0 |
| R/C | rs367774903 |
-0.132 | 1.0 | D | 0.591 | 0.468 | None | gnomAD-4.0.0 | 1.18496E-04 | None | None | None | None | N | None | 0 | 1.67218E-05 | None | 3.38662E-05 | 0 | None | 2.34698E-04 | 1.64853E-04 | 1.42506E-04 | 1.09977E-05 | 6.41375E-05 |
| R/H | rs374697274 |
-0.824 | 1.0 | N | 0.533 | 0.414 | None | gnomAD-2.1.1 | 4.86E-05 | None | None | None | None | N | None | 6.48E-05 | 2.91E-05 | None | 0 | 1.68843E-04 | None | 6.55E-05 | None | 0 | 3.58E-05 | 1.67168E-04 |
| R/H | rs374697274 |
-0.824 | 1.0 | N | 0.533 | 0.414 | None | gnomAD-3.1.2 | 6.58E-05 | None | None | None | None | N | None | 1.20715E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.42E-05 | 2.07039E-04 | 4.78469E-04 |
| R/H | rs374697274 |
-0.824 | 1.0 | N | 0.533 | 0.414 | None | gnomAD-4.0.0 | 1.04839E-04 | None | None | None | None | N | None | 9.35779E-05 | 3.34292E-05 | None | 0 | 6.71592E-05 | None | 0 | 8.24266E-04 | 1.21298E-04 | 5.49608E-05 | 6.41375E-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 | 0.7873 | likely_pathogenic | 0.7528 | pathogenic | -0.033 | Destabilizing | 0.996 | D | 0.466 | neutral | None | None | None | None | N |
| R/C | 0.3685 | ambiguous | 0.276 | benign | -0.311 | Destabilizing | 1.0 | D | 0.591 | neutral | D | 0.579444078 | None | None | N |
| R/D | 0.9404 | likely_pathogenic | 0.9148 | pathogenic | -0.142 | Destabilizing | 1.0 | D | 0.554 | neutral | None | None | None | None | N |
| R/E | 0.7445 | likely_pathogenic | 0.6835 | pathogenic | -0.037 | Destabilizing | 0.999 | D | 0.546 | neutral | None | None | None | None | N |
| R/F | 0.8802 | likely_pathogenic | 0.8371 | pathogenic | -0.132 | Destabilizing | 0.998 | D | 0.607 | neutral | None | None | None | None | N |
| R/G | 0.6864 | likely_pathogenic | 0.5937 | pathogenic | -0.268 | Destabilizing | 1.0 | D | 0.453 | neutral | N | 0.45594309 | None | None | N |
| R/H | 0.2437 | likely_benign | 0.1896 | benign | -0.848 | Destabilizing | 1.0 | D | 0.533 | neutral | N | 0.50967633 | None | None | N |
| R/I | 0.6281 | likely_pathogenic | 0.5726 | pathogenic | 0.563 | Stabilizing | 0.995 | D | 0.521 | neutral | None | None | None | None | N |
| R/K | 0.1998 | likely_benign | 0.1689 | benign | -0.099 | Destabilizing | 0.997 | D | 0.551 | neutral | None | None | None | None | N |
| R/L | 0.5564 | ambiguous | 0.5022 | ambiguous | 0.563 | Stabilizing | 0.413 | N | 0.32 | neutral | D | 0.536589501 | None | None | N |
| R/M | 0.656 | likely_pathogenic | 0.6148 | pathogenic | -0.078 | Destabilizing | 0.998 | D | 0.501 | neutral | None | None | None | None | N |
| R/N | 0.8872 | likely_pathogenic | 0.8426 | pathogenic | -0.071 | Destabilizing | 1.0 | D | 0.579 | neutral | None | None | None | None | N |
| R/P | 0.9803 | likely_pathogenic | 0.9704 | pathogenic | 0.385 | Stabilizing | 1.0 | D | 0.545 | neutral | D | 0.536589501 | None | None | N |
| R/Q | 0.2032 | likely_benign | 0.1683 | benign | -0.052 | Destabilizing | 1.0 | D | 0.611 | neutral | None | None | None | None | N |
| R/S | 0.8311 | likely_pathogenic | 0.7751 | pathogenic | -0.386 | Destabilizing | 1.0 | D | 0.435 | neutral | N | 0.495888689 | None | None | N |
| R/T | 0.656 | likely_pathogenic | 0.6061 | pathogenic | -0.121 | Destabilizing | 0.996 | D | 0.453 | neutral | None | None | None | None | N |
| R/V | 0.7147 | likely_pathogenic | 0.6613 | pathogenic | 0.385 | Stabilizing | 0.983 | D | 0.502 | neutral | None | None | None | None | N |
| R/W | 0.5169 | ambiguous | 0.4328 | ambiguous | -0.189 | Destabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | N |
| R/Y | 0.7258 | likely_pathogenic | 0.6562 | pathogenic | 0.215 | Stabilizing | 1.0 | D | 0.557 | 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.