Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32147 | 96664;96665;96666 | chr2:178543534;178543533;178543532 | chr2:179408261;179408260;179408259 |
| N2AB | 30506 | 91741;91742;91743 | chr2:178543534;178543533;178543532 | chr2:179408261;179408260;179408259 |
| N2A | 29579 | 88960;88961;88962 | chr2:178543534;178543533;178543532 | chr2:179408261;179408260;179408259 |
| N2B | 23082 | 69469;69470;69471 | chr2:178543534;178543533;178543532 | chr2:179408261;179408260;179408259 |
| Novex-1 | 23207 | 69844;69845;69846 | chr2:178543534;178543533;178543532 | chr2:179408261;179408260;179408259 |
| Novex-2 | 23274 | 70045;70046;70047 | chr2:178543534;178543533;178543532 | chr2:179408261;179408260;179408259 |
| 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 | rs774531768  |
-0.324 | 1.0 | N | 0.667 | 0.294 | 0.416202232284 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| A/V | rs774531768 |
-0.324 | 1.0 | N | 0.667 | 0.294 | 0.416202232284 | gnomAD-4.0.0 | 4.7805E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 8.33009E-05 | None | 0 | 0 | 0 | 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 | 0.7613 | likely_pathogenic | 0.7527 | pathogenic | -0.576 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| A/D | 0.8599 | likely_pathogenic | 0.8252 | pathogenic | -1.122 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | N | 0.508917956 | None | None | N |
| A/E | 0.7569 | likely_pathogenic | 0.7312 | pathogenic | -1.153 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| A/F | 0.7173 | likely_pathogenic | 0.6645 | pathogenic | -0.923 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| A/G | 0.2829 | likely_benign | 0.2638 | benign | -1.082 | Destabilizing | 1.0 | D | 0.597 | neutral | N | 0.49729824 | None | None | N |
| A/H | 0.871 | likely_pathogenic | 0.8635 | pathogenic | -1.182 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| A/I | 0.4993 | ambiguous | 0.4385 | ambiguous | -0.327 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| A/K | 0.8662 | likely_pathogenic | 0.8605 | pathogenic | -1.108 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| A/L | 0.4099 | ambiguous | 0.3868 | ambiguous | -0.327 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | N |
| A/M | 0.4032 | ambiguous | 0.3787 | ambiguous | -0.199 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| A/N | 0.6653 | likely_pathogenic | 0.6423 | pathogenic | -0.793 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| A/P | 0.7815 | likely_pathogenic | 0.7256 | pathogenic | -0.457 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | N | 0.492007063 | None | None | N |
| A/Q | 0.722 | likely_pathogenic | 0.7312 | pathogenic | -0.965 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| A/R | 0.8415 | likely_pathogenic | 0.839 | pathogenic | -0.697 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| A/S | 0.1602 | likely_benign | 0.1565 | benign | -1.104 | Destabilizing | 1.0 | D | 0.613 | neutral | N | 0.479653842 | None | None | N |
| A/T | 0.1951 | likely_benign | 0.1871 | benign | -1.051 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | N | 0.481192637 | None | None | N |
| A/V | 0.2416 | likely_benign | 0.2012 | benign | -0.457 | Destabilizing | 1.0 | D | 0.667 | neutral | N | 0.481653997 | None | None | N |
| A/W | 0.9467 | likely_pathogenic | 0.9373 | pathogenic | -1.287 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| A/Y | 0.8197 | likely_pathogenic | 0.7906 | pathogenic | -0.879 | Destabilizing | 1.0 | D | 0.695 | prob.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.