Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1323 | 4192;4193;4194 | chr2:178779115;178779114;178779113 | chr2:179643842;179643841;179643840 |
| N2AB | 1323 | 4192;4193;4194 | chr2:178779115;178779114;178779113 | chr2:179643842;179643841;179643840 |
| N2A | 1323 | 4192;4193;4194 | chr2:178779115;178779114;178779113 | chr2:179643842;179643841;179643840 |
| N2B | 1277 | 4054;4055;4056 | chr2:178779115;178779114;178779113 | chr2:179643842;179643841;179643840 |
| Novex-1 | 1277 | 4054;4055;4056 | chr2:178779115;178779114;178779113 | chr2:179643842;179643841;179643840 |
| Novex-2 | 1277 | 4054;4055;4056 | chr2:178779115;178779114;178779113 | chr2:179643842;179643841;179643840 |
| Novex-3 | 1323 | 4192;4193;4194 | chr2:178779115;178779114;178779113 | chr2:179643842;179643841;179643840 |
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/S | rs555618887  |
-0.71 | 0.978 | N | 0.454 | 0.262 | 0.229264304666 | gnomAD-2.1.1 | 5.6E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 4.57905E-04 | None | 0 | 0 | 0 |
| A/S | rs555618887 |
-0.71 | 0.978 | N | 0.454 | 0.262 | 0.229264304666 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.14422E-04 | 0 |
| A/S | rs555618887 |
-0.71 | 0.978 | N | 0.454 | 0.262 | 0.229264304666 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| A/S | rs555618887 |
-0.71 | 0.978 | N | 0.454 | 0.262 | 0.229264304666 | gnomAD-4.0.0 | 2.97443E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69501E-06 | 4.8323E-04 | 3.20031E-05 |
| A/T | rs555618887 |
-0.331 | 0.733 | N | 0.349 | 0.266 | 0.230578612272 | gnomAD-2.1.1 | 1.6E-05 | None | None | None | None | N | None | 0 | 1.16016E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/T | rs555618887 |
-0.331 | 0.733 | N | 0.349 | 0.266 | 0.230578612272 | gnomAD-4.0.0 | 2.737E-06 | None | None | None | None | N | None | 0 | 8.95015E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs774954394 |
0.764 | 0.733 | N | 0.358 | 0.408 | 0.408988072059 | gnomAD-2.1.1 | 4E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/V | rs774954394 |
0.764 | 0.733 | N | 0.358 | 0.408 | 0.408988072059 | gnomAD-4.0.0 | 1.59154E-06 | None | None | None | None | N | None | 0 | 2.28781E-05 | None | 0 | 0 | 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 | 0.74 | likely_pathogenic | 0.738 | pathogenic | -0.196 | Destabilizing | 1.0 | D | 0.638 | neutral | None | None | None | None | N |
| A/D | 0.9702 | likely_pathogenic | 0.9694 | pathogenic | -1.578 | Destabilizing | 0.998 | D | 0.709 | prob.delet. | N | 0.483203616 | None | None | N |
| A/E | 0.9248 | likely_pathogenic | 0.9294 | pathogenic | -1.415 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | N |
| A/F | 0.7659 | likely_pathogenic | 0.7874 | pathogenic | -0.526 | Destabilizing | 0.999 | D | 0.757 | deleterious | None | None | None | None | N |
| A/G | 0.5471 | ambiguous | 0.5607 | ambiguous | -1.067 | Destabilizing | 0.994 | D | 0.467 | neutral | N | 0.499531806 | None | None | N |
| A/H | 0.9139 | likely_pathogenic | 0.9163 | pathogenic | -1.476 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| A/I | 0.6265 | likely_pathogenic | 0.6449 | pathogenic | 0.422 | Stabilizing | 0.983 | D | 0.592 | neutral | None | None | None | None | N |
| A/K | 0.9778 | likely_pathogenic | 0.9781 | pathogenic | -0.697 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| A/L | 0.5903 | likely_pathogenic | 0.6112 | pathogenic | 0.422 | Stabilizing | 0.983 | D | 0.489 | neutral | None | None | None | None | N |
| A/M | 0.6584 | likely_pathogenic | 0.6839 | pathogenic | 0.416 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| A/N | 0.875 | likely_pathogenic | 0.8772 | pathogenic | -0.826 | Destabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | N |
| A/P | 0.9972 | likely_pathogenic | 0.9969 | pathogenic | 0.105 | Stabilizing | 0.999 | D | 0.689 | prob.neutral | N | 0.512583378 | None | None | N |
| A/Q | 0.8311 | likely_pathogenic | 0.8342 | pathogenic | -0.715 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| A/R | 0.9248 | likely_pathogenic | 0.9262 | pathogenic | -0.761 | Destabilizing | 0.999 | D | 0.706 | prob.neutral | None | None | None | None | N |
| A/S | 0.2135 | likely_benign | 0.2093 | benign | -1.197 | Destabilizing | 0.978 | D | 0.454 | neutral | N | 0.351651762 | None | None | N |
| A/T | 0.3175 | likely_benign | 0.3229 | benign | -0.921 | Destabilizing | 0.733 | D | 0.349 | neutral | N | 0.342080279 | None | None | N |
| A/V | 0.3835 | ambiguous | 0.4483 | ambiguous | 0.105 | Stabilizing | 0.733 | D | 0.358 | neutral | N | 0.438312227 | None | None | N |
| A/W | 0.9746 | likely_pathogenic | 0.9755 | pathogenic | -1.271 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| A/Y | 0.8933 | likely_pathogenic | 0.903 | pathogenic | -0.619 | Destabilizing | 1.0 | D | 0.757 | deleterious | 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.