Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9761 | 29506;29507;29508 | chr2:178706593;178706592;178706591 | chr2:179571320;179571319;179571318 |
| N2AB | 9444 | 28555;28556;28557 | chr2:178706593;178706592;178706591 | chr2:179571320;179571319;179571318 |
| N2A | 8517 | 25774;25775;25776 | chr2:178706593;178706592;178706591 | chr2:179571320;179571319;179571318 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs757275707  |
0.12 | 0.022 | None | 0.172 | 0.134 | 0.186928172975 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/A | rs757275707 |
0.12 | 0.022 | None | 0.172 | 0.134 | 0.186928172975 | gnomAD-4.0.0 | 1.59097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43275E-05 | 0 |
| T/S | rs753921516 |
-1.106 | 0.051 | None | 0.213 | 0.192 | 0.247872288689 | gnomAD-2.1.1 | 8.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.56E-05 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/S | rs753921516 |
-1.106 | 0.051 | None | 0.213 | 0.192 | 0.247872288689 | gnomAD-4.0.0 | 3.18199E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77285E-05 | None | 0 | 0 | 0 | 1.43279E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1901 | likely_benign | 0.0969 | benign | -0.498 | Destabilizing | 0.022 | N | 0.172 | neutral | None | None | None | None | N |
| T/C | 0.665 | likely_pathogenic | 0.5543 | ambiguous | -1.373 | Destabilizing | 0.998 | D | 0.567 | neutral | None | None | None | None | N |
| T/D | 0.9973 | likely_pathogenic | 0.9861 | pathogenic | -2.895 | Highly Destabilizing | 0.842 | D | 0.552 | neutral | None | None | None | None | N |
| T/E | 0.9956 | likely_pathogenic | 0.9762 | pathogenic | -2.752 | Highly Destabilizing | 0.842 | D | 0.531 | neutral | None | None | None | None | N |
| T/F | 0.9895 | likely_pathogenic | 0.9254 | pathogenic | -0.731 | Destabilizing | 0.974 | D | 0.611 | neutral | None | None | None | None | N |
| T/G | 0.8885 | likely_pathogenic | 0.7047 | pathogenic | -0.719 | Destabilizing | 0.728 | D | 0.496 | neutral | None | None | None | None | N |
| T/H | 0.993 | likely_pathogenic | 0.9629 | pathogenic | -0.961 | Destabilizing | 0.998 | D | 0.552 | neutral | None | None | None | None | N |
| T/I | 0.7209 | likely_pathogenic | 0.4144 | ambiguous | 0.024 | Stabilizing | 0.454 | N | 0.486 | neutral | None | None | None | None | N |
| T/K | 0.9922 | likely_pathogenic | 0.9589 | pathogenic | -0.624 | Destabilizing | 0.842 | D | 0.545 | neutral | None | None | None | None | N |
| T/L | 0.6138 | likely_pathogenic | 0.3405 | ambiguous | 0.024 | Stabilizing | 0.525 | D | 0.471 | neutral | None | None | None | None | N |
| T/M | 0.5796 | likely_pathogenic | 0.2932 | benign | -0.276 | Destabilizing | 0.974 | D | 0.589 | neutral | None | None | None | None | N |
| T/N | 0.9414 | likely_pathogenic | 0.7972 | pathogenic | -1.568 | Destabilizing | 0.801 | D | 0.571 | neutral | None | None | None | None | N |
| T/P | 0.8623 | likely_pathogenic | 0.6068 | pathogenic | -0.125 | Destabilizing | 0.966 | D | 0.618 | neutral | None | None | None | None | N |
| T/Q | 0.9863 | likely_pathogenic | 0.9424 | pathogenic | -1.505 | Destabilizing | 0.974 | D | 0.617 | neutral | None | None | None | None | N |
| T/R | 0.9842 | likely_pathogenic | 0.9244 | pathogenic | -0.633 | Destabilizing | 0.949 | D | 0.621 | neutral | None | None | None | None | N |
| T/S | 0.6346 | likely_pathogenic | 0.3802 | ambiguous | -1.318 | Destabilizing | 0.051 | N | 0.213 | neutral | None | None | None | None | N |
| T/V | 0.322 | likely_benign | 0.1987 | benign | -0.125 | Destabilizing | 0.007 | N | 0.155 | neutral | None | None | None | None | N |
| T/W | 0.9994 | likely_pathogenic | 0.9946 | pathogenic | -1.175 | Destabilizing | 0.998 | D | 0.542 | neutral | None | None | None | None | N |
| T/Y | 0.9964 | likely_pathogenic | 0.972 | pathogenic | -0.619 | Destabilizing | 0.991 | D | 0.619 | 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.