Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28436 | 85531;85532;85533 | chr2:178560826;178560825;178560824 | chr2:179425553;179425552;179425551 |
| N2AB | 26795 | 80608;80609;80610 | chr2:178560826;178560825;178560824 | chr2:179425553;179425552;179425551 |
| N2A | 25868 | 77827;77828;77829 | chr2:178560826;178560825;178560824 | chr2:179425553;179425552;179425551 |
| N2B | 19371 | 58336;58337;58338 | chr2:178560826;178560825;178560824 | chr2:179425553;179425552;179425551 |
| Novex-1 | 19496 | 58711;58712;58713 | chr2:178560826;178560825;178560824 | chr2:179425553;179425552;179425551 |
| Novex-2 | 19563 | 58912;58913;58914 | chr2:178560826;178560825;178560824 | chr2:179425553;179425552;179425551 |
| 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 | rs1559291915  |
None | 0.999 | N | 0.72 | 0.371 | 0.48095081912 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| A/V | rs1559291915 |
None | 0.999 | N | 0.72 | 0.371 | 0.48095081912 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/V | rs1559291915 |
None | 0.999 | N | 0.72 | 0.371 | 0.48095081912 | gnomAD-4.0.0 | 6.57186E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46985E-05 | 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 | 0.607 | likely_pathogenic | 0.6528 | pathogenic | -0.941 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | I |
| A/D | 0.8969 | likely_pathogenic | 0.9043 | pathogenic | -0.5 | Destabilizing | 0.999 | D | 0.741 | deleterious | D | 0.525071753 | None | None | I |
| A/E | 0.8602 | likely_pathogenic | 0.8691 | pathogenic | -0.641 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | I |
| A/F | 0.5903 | likely_pathogenic | 0.6403 | pathogenic | -0.966 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| A/G | 0.1805 | likely_benign | 0.1786 | benign | -0.315 | Destabilizing | 0.434 | N | 0.471 | neutral | N | 0.504315505 | None | None | I |
| A/H | 0.8476 | likely_pathogenic | 0.8762 | pathogenic | -0.27 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | I |
| A/I | 0.7031 | likely_pathogenic | 0.7125 | pathogenic | -0.507 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| A/K | 0.9383 | likely_pathogenic | 0.9471 | pathogenic | -0.564 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| A/L | 0.4752 | ambiguous | 0.4959 | ambiguous | -0.507 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | I |
| A/M | 0.5843 | likely_pathogenic | 0.5991 | pathogenic | -0.652 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| A/N | 0.7828 | likely_pathogenic | 0.7915 | pathogenic | -0.325 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| A/P | 0.9304 | likely_pathogenic | 0.9388 | pathogenic | -0.421 | Destabilizing | 1.0 | D | 0.756 | deleterious | D | 0.536428058 | None | None | I |
| A/Q | 0.8114 | likely_pathogenic | 0.8265 | pathogenic | -0.559 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | I |
| A/R | 0.8621 | likely_pathogenic | 0.8812 | pathogenic | -0.161 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | I |
| A/S | 0.1643 | likely_benign | 0.1596 | benign | -0.528 | Destabilizing | 0.996 | D | 0.624 | neutral | N | 0.516898013 | None | None | I |
| A/T | 0.3148 | likely_benign | 0.317 | benign | -0.595 | Destabilizing | 0.999 | D | 0.73 | prob.delet. | N | 0.521776389 | None | None | I |
| A/V | 0.3809 | ambiguous | 0.3859 | ambiguous | -0.421 | Destabilizing | 0.999 | D | 0.72 | prob.delet. | N | 0.490191414 | None | None | I |
| A/W | 0.927 | likely_pathogenic | 0.9427 | pathogenic | -1.045 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
| A/Y | 0.7949 | likely_pathogenic | 0.8365 | pathogenic | -0.755 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
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.