Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35474 | 106645;106646;106647 | chr2:178530071;178530070;178530069 | chr2:179394798;179394797;179394796 |
| N2AB | 33833 | 101722;101723;101724 | chr2:178530071;178530070;178530069 | chr2:179394798;179394797;179394796 |
| N2A | 32906 | 98941;98942;98943 | chr2:178530071;178530070;178530069 | chr2:179394798;179394797;179394796 |
| N2B | 26409 | 79450;79451;79452 | chr2:178530071;178530070;178530069 | chr2:179394798;179394797;179394796 |
| Novex-1 | 26534 | 79825;79826;79827 | chr2:178530071;178530070;178530069 | chr2:179394798;179394797;179394796 |
| Novex-2 | 26601 | 80026;80027;80028 | chr2:178530071;178530070;178530069 | chr2:179394798;179394797;179394796 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | None | None | None | N | 0.162 | 0.083 | 0.0611884634855 | gnomAD-4.0.0 | 1.59814E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.03251E-05 |
| G/V | rs747075406  |
0.345 | None | N | 0.477 | 0.107 | 0.128392430309 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.36E-05 | None | 0 | 0 | 0 |
| G/V | rs747075406 |
0.345 | None | N | 0.477 | 0.107 | 0.128392430309 | gnomAD-4.0.0 | 3.19628E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.9074E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.0651 | likely_benign | 0.0692 | benign | -0.443 | Destabilizing | None | N | 0.162 | neutral | N | 0.493730365 | None | None | N |
| G/C | 0.1347 | likely_benign | 0.1312 | benign | -0.615 | Destabilizing | 0.448 | N | 0.676 | prob.neutral | None | None | None | None | N |
| G/D | 0.1173 | likely_benign | 0.1195 | benign | -0.745 | Destabilizing | 0.015 | N | 0.597 | neutral | None | None | None | None | N |
| G/E | 0.1039 | likely_benign | 0.1084 | benign | -0.741 | Destabilizing | None | N | 0.461 | neutral | N | 0.474104454 | None | None | N |
| G/F | 0.1996 | likely_benign | 0.2062 | benign | -0.649 | Destabilizing | 0.096 | N | 0.705 | prob.neutral | None | None | None | None | N |
| G/H | 0.1935 | likely_benign | 0.1913 | benign | -1.228 | Destabilizing | 0.177 | N | 0.663 | neutral | None | None | None | None | N |
| G/I | 0.0664 | likely_benign | 0.066 | benign | 0.125 | Stabilizing | None | N | 0.609 | neutral | None | None | None | None | N |
| G/K | 0.1925 | likely_benign | 0.1926 | benign | -0.788 | Destabilizing | 0.006 | N | 0.599 | neutral | None | None | None | None | N |
| G/L | 0.1234 | likely_benign | 0.1238 | benign | 0.125 | Stabilizing | 0.002 | N | 0.652 | neutral | None | None | None | None | N |
| G/M | 0.1481 | likely_benign | 0.1437 | benign | 0.013 | Stabilizing | 0.096 | N | 0.688 | prob.neutral | None | None | None | None | N |
| G/N | 0.1266 | likely_benign | 0.1208 | benign | -0.565 | Destabilizing | 0.029 | N | 0.521 | neutral | None | None | None | None | N |
| G/P | 0.6387 | likely_pathogenic | 0.6312 | pathogenic | -0.02 | Destabilizing | 0.029 | N | 0.685 | prob.neutral | None | None | None | None | N |
| G/Q | 0.1512 | likely_benign | 0.1586 | benign | -0.627 | Destabilizing | 0.015 | N | 0.687 | prob.neutral | None | None | None | None | N |
| G/R | 0.127 | likely_benign | 0.1312 | benign | -0.718 | Destabilizing | None | N | 0.6 | neutral | N | 0.454691974 | None | None | N |
| G/S | 0.067 | likely_benign | 0.0667 | benign | -0.908 | Destabilizing | None | N | 0.177 | neutral | None | None | None | None | N |
| G/T | 0.0741 | likely_benign | 0.0667 | benign | -0.808 | Destabilizing | 0.006 | N | 0.598 | neutral | None | None | None | None | N |
| G/V | 0.061 | likely_benign | 0.0635 | benign | -0.02 | Destabilizing | None | N | 0.477 | neutral | N | 0.447112641 | None | None | N |
| G/W | 0.1944 | likely_benign | 0.2019 | benign | -1.151 | Destabilizing | 0.651 | D | 0.658 | neutral | N | 0.476704829 | None | None | N |
| G/Y | 0.1697 | likely_benign | 0.1693 | benign | -0.627 | Destabilizing | 0.177 | N | 0.693 | 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.