Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30723 | 92392;92393;92394 | chr2:178549459;178549458;178549457 | chr2:179414186;179414185;179414184 |
| N2AB | 29082 | 87469;87470;87471 | chr2:178549459;178549458;178549457 | chr2:179414186;179414185;179414184 |
| N2A | 28155 | 84688;84689;84690 | chr2:178549459;178549458;178549457 | chr2:179414186;179414185;179414184 |
| N2B | 21658 | 65197;65198;65199 | chr2:178549459;178549458;178549457 | chr2:179414186;179414185;179414184 |
| Novex-1 | 21783 | 65572;65573;65574 | chr2:178549459;178549458;178549457 | chr2:179414186;179414185;179414184 |
| Novex-2 | 21850 | 65773;65774;65775 | chr2:178549459;178549458;178549457 | chr2:179414186;179414185;179414184 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/R | None | None | 1.0 | D | 0.931 | 0.746 | 0.807518484997 | gnomAD-4.0.0 | 6.88537E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.04418E-07 | 0 | 0 |
| P/S | rs758537709  |
-2.849 | 1.0 | D | 0.845 | 0.861 | None | gnomAD-2.1.1 | 6.18E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 1.21971E-04 | 1.03339E-04 | 1.4339E-04 |
| P/S | rs758537709 |
-2.849 | 1.0 | D | 0.845 | 0.861 | None | gnomAD-3.1.2 | 9.2E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 1.88537E-04 | 0 | 1.76414E-04 | 0 | 0 |
| P/S | rs758537709 |
-2.849 | 1.0 | D | 0.845 | 0.861 | None |
Evila (2014)
Lopez-Bravo (2021)
| None |
TMD 
|
comp het with 35927delinsEVTW>VKEK (FINmaj) / hom | None | None | N | Genetic analysis of genes in patients with previously reported TTN variants; found in single patient comp het with TMD-associated indel FINmaj (EVTW35927delinsVKEK); more severe TMD than others in phenotype; subsequent identification in single patient with distal myopathy of lower limbs and DCM; homozygous in affected patient, heterozygous in both unaffected parents | None | None | None | None | None | None | None | None | None | None | None |
| P/S | rs758537709 |
-2.849 | 1.0 | D | 0.845 | 0.861 | None | gnomAD-4.0.0 | 9.53693E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.72788E-04 | 0 | 1.18445E-04 | 0 | 4.84121E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.6274 | likely_pathogenic | 0.6587 | pathogenic | -2.258 | Highly Destabilizing | 1.0 | D | 0.777 | deleterious | D | 0.549575698 | None | None | N |
| P/C | 0.8736 | likely_pathogenic | 0.9217 | pathogenic | -2.158 | Highly Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| P/D | 0.9988 | likely_pathogenic | 0.9991 | pathogenic | -3.412 | Highly Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| P/E | 0.9974 | likely_pathogenic | 0.9981 | pathogenic | -3.233 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| P/F | 0.9988 | likely_pathogenic | 0.9991 | pathogenic | -1.241 | Destabilizing | 1.0 | D | 0.919 | deleterious | None | None | None | None | N |
| P/G | 0.9823 | likely_pathogenic | 0.9867 | pathogenic | -2.721 | Highly Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| P/H | 0.9964 | likely_pathogenic | 0.9974 | pathogenic | -2.311 | Highly Destabilizing | 1.0 | D | 0.885 | deleterious | D | 0.586798166 | None | None | N |
| P/I | 0.9596 | likely_pathogenic | 0.9752 | pathogenic | -0.969 | Destabilizing | 1.0 | D | 0.933 | deleterious | None | None | None | None | N |
| P/K | 0.9982 | likely_pathogenic | 0.9987 | pathogenic | -1.921 | Destabilizing | 1.0 | D | 0.834 | deleterious | None | None | None | None | N |
| P/L | 0.905 | likely_pathogenic | 0.9251 | pathogenic | -0.969 | Destabilizing | 1.0 | D | 0.911 | deleterious | D | 0.573667434 | None | None | N |
| P/M | 0.9822 | likely_pathogenic | 0.9869 | pathogenic | -1.276 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| P/N | 0.9982 | likely_pathogenic | 0.9987 | pathogenic | -2.276 | Highly Destabilizing | 1.0 | D | 0.928 | deleterious | None | None | None | None | N |
| P/Q | 0.9938 | likely_pathogenic | 0.9953 | pathogenic | -2.19 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| P/R | 0.9929 | likely_pathogenic | 0.9946 | pathogenic | -1.628 | Destabilizing | 1.0 | D | 0.931 | deleterious | D | 0.586291187 | None | None | N |
| P/S | 0.956 | likely_pathogenic | 0.965 | pathogenic | -2.759 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | D | 0.556919532 | None | None | N |
| P/T | 0.9102 | likely_pathogenic | 0.9398 | pathogenic | -2.462 | Highly Destabilizing | 1.0 | D | 0.839 | deleterious | D | 0.574427902 | None | None | N |
| P/V | 0.8495 | likely_pathogenic | 0.9052 | pathogenic | -1.376 | Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| P/W | 0.9996 | likely_pathogenic | 0.9998 | pathogenic | -1.741 | Destabilizing | 1.0 | D | 0.885 | deleterious | None | None | None | None | N |
| P/Y | 0.9994 | likely_pathogenic | 0.9995 | pathogenic | -1.462 | Destabilizing | 1.0 | D | 0.924 | 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.