Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21681 | 65266;65267;65268 | chr2:178584510;178584509;178584508 | chr2:179449237;179449236;179449235 |
| N2AB | 20040 | 60343;60344;60345 | chr2:178584510;178584509;178584508 | chr2:179449237;179449236;179449235 |
| N2A | 19113 | 57562;57563;57564 | chr2:178584510;178584509;178584508 | chr2:179449237;179449236;179449235 |
| N2B | 12616 | 38071;38072;38073 | chr2:178584510;178584509;178584508 | chr2:179449237;179449236;179449235 |
| Novex-1 | 12741 | 38446;38447;38448 | chr2:178584510;178584509;178584508 | chr2:179449237;179449236;179449235 |
| Novex-2 | 12808 | 38647;38648;38649 | chr2:178584510;178584509;178584508 | chr2:179449237;179449236;179449235 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/V | rs192371243  |
0.524 | 0.97 | N | 0.725 | 0.436 | None | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 5.81E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/V | rs192371243 |
0.524 | 0.97 | N | 0.725 | 0.436 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/V | rs192371243 |
0.524 | 0.97 | N | 0.725 | 0.436 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| D/V | rs192371243 |
0.524 | 0.97 | N | 0.725 | 0.436 | None | gnomAD-4.0.0 | 2.47946E-06 | None | None | None | None | N | None | 0 | 3.33456E-05 | None | 0 | 0 | None | 0 | 0 | 8.47797E-07 | 0 | 1.60133E-05 |
| D/Y | None | None | 0.99 | N | 0.773 | 0.337 | 0.495506531988 | gnomAD-4.0.0 | 1.5925E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43328E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2956 | likely_benign | 0.2814 | benign | -0.41 | Destabilizing | 0.822 | D | 0.607 | neutral | N | 0.487523964 | None | None | N |
| D/C | 0.7757 | likely_pathogenic | 0.7614 | pathogenic | -0.256 | Destabilizing | 0.998 | D | 0.791 | deleterious | None | None | None | None | N |
| D/E | 0.1713 | likely_benign | 0.1568 | benign | -0.789 | Destabilizing | 0.025 | N | 0.159 | neutral | N | 0.410215186 | None | None | N |
| D/F | 0.8254 | likely_pathogenic | 0.8047 | pathogenic | -0.338 | Destabilizing | 0.993 | D | 0.77 | deleterious | None | None | None | None | N |
| D/G | 0.2842 | likely_benign | 0.2813 | benign | -0.73 | Destabilizing | 0.698 | D | 0.525 | neutral | N | 0.512016976 | None | None | N |
| D/H | 0.4472 | ambiguous | 0.4442 | ambiguous | -0.817 | Destabilizing | 0.97 | D | 0.696 | prob.neutral | N | 0.471977896 | None | None | N |
| D/I | 0.6222 | likely_pathogenic | 0.5851 | pathogenic | 0.421 | Stabilizing | 0.978 | D | 0.777 | deleterious | None | None | None | None | N |
| D/K | 0.569 | likely_pathogenic | 0.5744 | pathogenic | -0.711 | Destabilizing | 0.86 | D | 0.535 | neutral | None | None | None | None | N |
| D/L | 0.584 | likely_pathogenic | 0.5519 | ambiguous | 0.421 | Stabilizing | 0.978 | D | 0.727 | prob.delet. | None | None | None | None | N |
| D/M | 0.7758 | likely_pathogenic | 0.7447 | pathogenic | 0.857 | Stabilizing | 0.998 | D | 0.763 | deleterious | None | None | None | None | N |
| D/N | 0.1546 | likely_benign | 0.1541 | benign | -0.915 | Destabilizing | 0.014 | N | 0.299 | neutral | N | 0.457374415 | None | None | N |
| D/P | 0.9478 | likely_pathogenic | 0.9472 | pathogenic | 0.169 | Stabilizing | 0.993 | D | 0.691 | prob.neutral | None | None | None | None | N |
| D/Q | 0.4234 | ambiguous | 0.4104 | ambiguous | -0.784 | Destabilizing | 0.86 | D | 0.513 | neutral | None | None | None | None | N |
| D/R | 0.6207 | likely_pathogenic | 0.6261 | pathogenic | -0.62 | Destabilizing | 0.956 | D | 0.718 | prob.delet. | None | None | None | None | N |
| D/S | 0.2047 | likely_benign | 0.2009 | benign | -1.163 | Destabilizing | 0.754 | D | 0.435 | neutral | None | None | None | None | N |
| D/T | 0.3873 | ambiguous | 0.3619 | ambiguous | -0.919 | Destabilizing | 0.86 | D | 0.597 | neutral | None | None | None | None | N |
| D/V | 0.3959 | ambiguous | 0.3713 | ambiguous | 0.169 | Stabilizing | 0.97 | D | 0.725 | prob.delet. | N | 0.493257857 | None | None | N |
| D/W | 0.9405 | likely_pathogenic | 0.9314 | pathogenic | -0.337 | Destabilizing | 0.998 | D | 0.759 | deleterious | None | None | None | None | N |
| D/Y | 0.4361 | ambiguous | 0.4168 | ambiguous | -0.184 | Destabilizing | 0.99 | D | 0.773 | deleterious | N | 0.468610534 | 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.