Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19793 | 59602;59603;59604 | chr2:178592628;178592627;178592626 | chr2:179457355;179457354;179457353 |
| N2AB | 18152 | 54679;54680;54681 | chr2:178592628;178592627;178592626 | chr2:179457355;179457354;179457353 |
| N2A | 17225 | 51898;51899;51900 | chr2:178592628;178592627;178592626 | chr2:179457355;179457354;179457353 |
| N2B | 10728 | 32407;32408;32409 | chr2:178592628;178592627;178592626 | chr2:179457355;179457354;179457353 |
| Novex-1 | 10853 | 32782;32783;32784 | chr2:178592628;178592627;178592626 | chr2:179457355;179457354;179457353 |
| Novex-2 | 10920 | 32983;32984;32985 | chr2:178592628;178592627;178592626 | chr2:179457355;179457354;179457353 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/V | rs1433039414  |
-0.252 | 0.001 | N | 0.419 | 0.175 | 0.278143212241 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| A/V | rs1433039414 |
-0.252 | 0.001 | N | 0.419 | 0.175 | 0.278143212241 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| A/V | rs1433039414 |
-0.252 | 0.001 | N | 0.419 | 0.175 | 0.278143212241 | gnomAD-4.0.0 | 5.12832E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.57827E-06 | 0 | 0 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7243 | likely_pathogenic | 0.7873 | pathogenic | -0.754 | Destabilizing | 0.944 | D | 0.578 | neutral | None | None | None | None | N |
| A/D | 0.7604 | likely_pathogenic | 0.8713 | pathogenic | -0.83 | Destabilizing | 0.69 | D | 0.588 | neutral | None | None | None | None | N |
| A/E | 0.5961 | likely_pathogenic | 0.7507 | pathogenic | -0.983 | Destabilizing | 0.324 | N | 0.543 | neutral | N | 0.413322567 | None | None | N |
| A/F | 0.6454 | likely_pathogenic | 0.7356 | pathogenic | -1.031 | Destabilizing | 0.818 | D | 0.621 | neutral | None | None | None | None | N |
| A/G | 0.2678 | likely_benign | 0.3183 | benign | -0.544 | Destabilizing | 0.324 | N | 0.543 | neutral | N | 0.451976956 | None | None | N |
| A/H | 0.7597 | likely_pathogenic | 0.8469 | pathogenic | -0.623 | Destabilizing | 0.981 | D | 0.583 | neutral | None | None | None | None | N |
| A/I | 0.4681 | ambiguous | 0.6056 | pathogenic | -0.448 | Destabilizing | 0.241 | N | 0.539 | neutral | None | None | None | None | N |
| A/K | 0.7727 | likely_pathogenic | 0.8809 | pathogenic | -0.898 | Destabilizing | 0.388 | N | 0.543 | neutral | None | None | None | None | N |
| A/L | 0.2937 | likely_benign | 0.4024 | ambiguous | -0.448 | Destabilizing | 0.241 | N | 0.543 | neutral | None | None | None | None | N |
| A/M | 0.4068 | ambiguous | 0.5013 | ambiguous | -0.372 | Destabilizing | 0.818 | D | 0.571 | neutral | None | None | None | None | N |
| A/N | 0.5461 | ambiguous | 0.6478 | pathogenic | -0.51 | Destabilizing | 0.69 | D | 0.6 | neutral | None | None | None | None | N |
| A/P | 0.6062 | likely_pathogenic | 0.7624 | pathogenic | -0.419 | Destabilizing | 0.001 | N | 0.399 | neutral | N | 0.320068476 | None | None | N |
| A/Q | 0.5005 | ambiguous | 0.6314 | pathogenic | -0.826 | Destabilizing | 0.818 | D | 0.596 | neutral | None | None | None | None | N |
| A/R | 0.6612 | likely_pathogenic | 0.8037 | pathogenic | -0.364 | Destabilizing | 0.69 | D | 0.586 | neutral | None | None | None | None | N |
| A/S | 0.1542 | likely_benign | 0.1769 | benign | -0.686 | Destabilizing | 0.193 | N | 0.563 | neutral | N | 0.355794416 | None | None | N |
| A/T | 0.1975 | likely_benign | 0.2759 | benign | -0.766 | Destabilizing | 0.001 | N | 0.234 | neutral | N | 0.383693094 | None | None | N |
| A/V | 0.2236 | likely_benign | 0.3349 | benign | -0.419 | Destabilizing | 0.001 | N | 0.419 | neutral | N | 0.449549939 | None | None | N |
| A/W | 0.9067 | likely_pathogenic | 0.947 | pathogenic | -1.183 | Destabilizing | 0.981 | D | 0.645 | neutral | None | None | None | None | N |
| A/Y | 0.7698 | likely_pathogenic | 0.8437 | pathogenic | -0.847 | Destabilizing | 0.818 | D | 0.615 | 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.