Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 10092 | 30499;30500;30501 | chr2:178702613;178702612;178702611 | chr2:179567340;179567339;179567338 |
| N2AB | 9775 | 29548;29549;29550 | chr2:178702613;178702612;178702611 | chr2:179567340;179567339;179567338 |
| N2A | 8848 | 26767;26768;26769 | chr2:178702613;178702612;178702611 | chr2:179567340;179567339;179567338 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/L | None | None | 0.473 | None | 0.475 | 0.344 | 0.550759897685 | gnomAD-4.0.0 | 1.59086E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77239E-05 | None | 0 | 0 | 0 | 0 | 0 |
| H/R | rs1311702740  |
None | 0.002 | None | 0.205 | 0.194 | 0.226586394389 | gnomAD-4.0.0 | 3.18172E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.715E-06 | 0 | 0 |
| H/Y | rs72650011 |
1.114 | 0.006 | None | 0.247 | 0.416 | None | gnomAD-2.1.1 | 4.04131E-03 | None | None | None | None | N | None | 2.8928E-04 | 5.08992E-04 | None | 1.1592E-03 | 0 | None | 2.71242E-03 | None | 8.83293E-03 | 6.01293E-03 | 2.93953E-03 |
| H/Y | rs72650011 |
1.114 | 0.006 | None | 0.247 | 0.416 | None | gnomAD-3.1.2 | 3.6088E-03 | None | None | None | None | N | None | 4.82928E-04 | 1.11286E-03 | 1.0989E-03 | 1.1534E-03 | 0 | None | 1.06543E-02 | 0 | 5.58659E-03 | 2.69263E-03 | 4.78469E-04 |
| H/Y | rs72650011 |
1.114 | 0.006 | None | 0.247 | 0.416 | None | 1000 genomes | 1.19808E-03 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 2E-03 | None | None | None | 3.1E-03 | None |
| H/Y | rs72650011 |
1.114 | 0.006 | None | 0.247 | 0.416 | None |
Taylor (2011)
Costa (2021)
| None |
ARVC 
|
het | None | None | N | Genetic analysis of TTN in 38 ARVC families, incomplete penetrance; subsequent identification of variant in desmoglein-2 (DSG2: c.152G>C) which co-segregates fully with condition in original affected individuals (n = 2) | None | None | None | None | None | None | None | None | None | None | None |
| H/Y | rs72650011 |
1.114 | 0.006 | None | 0.247 | 0.416 | None | gnomAD-4.0.0 | 3.48525E-03 | None | None | None | None | N | None | 4.26576E-04 | 7.66411E-04 | None | 8.7826E-04 | 4.45534E-05 | None | 9.03012E-03 | 1.64962E-03 | 3.84788E-03 | 2.29469E-03 | 2.89665E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.9563 | likely_pathogenic | 0.933 | pathogenic | 0.415 | Stabilizing | 0.495 | N | 0.425 | neutral | None | None | None | None | N |
| H/C | 0.8564 | likely_pathogenic | 0.8415 | pathogenic | 0.908 | Stabilizing | 0.995 | D | 0.503 | neutral | None | None | None | None | N |
| H/D | 0.8326 | likely_pathogenic | 0.7338 | pathogenic | 0.121 | Stabilizing | 0.473 | N | 0.445 | neutral | None | None | None | None | N |
| H/E | 0.9269 | likely_pathogenic | 0.8723 | pathogenic | 0.13 | Stabilizing | 0.495 | N | 0.311 | neutral | None | None | None | None | N |
| H/F | 0.8047 | likely_pathogenic | 0.7722 | pathogenic | 0.893 | Stabilizing | 0.543 | D | 0.479 | neutral | None | None | None | None | N |
| H/G | 0.7712 | likely_pathogenic | 0.6596 | pathogenic | 0.148 | Stabilizing | 0.495 | N | 0.423 | neutral | None | None | None | None | N |
| H/I | 0.9886 | likely_pathogenic | 0.9839 | pathogenic | 1.085 | Stabilizing | 0.893 | D | 0.52 | neutral | None | None | None | None | N |
| H/K | 0.7327 | likely_pathogenic | 0.6432 | pathogenic | 0.393 | Stabilizing | 0.329 | N | 0.421 | neutral | None | None | None | None | N |
| H/L | 0.7631 | likely_pathogenic | 0.7097 | pathogenic | 1.085 | Stabilizing | 0.473 | N | 0.475 | neutral | None | None | None | None | N |
| H/M | 0.9514 | likely_pathogenic | 0.9384 | pathogenic | 0.908 | Stabilizing | 0.981 | D | 0.503 | neutral | None | None | None | None | N |
| H/N | 0.4355 | ambiguous | 0.3192 | benign | 0.509 | Stabilizing | 0.01 | N | 0.248 | neutral | None | None | None | None | N |
| H/P | 0.9723 | likely_pathogenic | 0.961 | pathogenic | 0.888 | Stabilizing | 0.975 | D | 0.49 | neutral | None | None | None | None | N |
| H/Q | 0.7586 | likely_pathogenic | 0.6644 | pathogenic | 0.567 | Stabilizing | 0.642 | D | 0.344 | neutral | None | None | None | None | N |
| H/R | 0.4765 | ambiguous | 0.4169 | ambiguous | -0.147 | Destabilizing | 0.002 | N | 0.205 | neutral | None | None | None | None | N |
| H/S | 0.8722 | likely_pathogenic | 0.7963 | pathogenic | 0.597 | Stabilizing | 0.495 | N | 0.415 | neutral | None | None | None | None | N |
| H/T | 0.9407 | likely_pathogenic | 0.9053 | pathogenic | 0.699 | Stabilizing | 0.704 | D | 0.466 | neutral | None | None | None | None | N |
| H/V | 0.9779 | likely_pathogenic | 0.9719 | pathogenic | 0.888 | Stabilizing | 0.704 | D | 0.52 | neutral | None | None | None | None | N |
| H/W | 0.8771 | likely_pathogenic | 0.8528 | pathogenic | 0.831 | Stabilizing | 0.985 | D | 0.488 | neutral | None | None | None | None | N |
| H/Y | 0.4275 | ambiguous | 0.3739 | ambiguous | 1.179 | Stabilizing | 0.006 | N | 0.247 | 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.