Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4854 | 14785;14786;14787 | chr2:178735886;178735885;178735884 | chr2:179600613;179600612;179600611 |
| N2AB | 4537 | 13834;13835;13836 | chr2:178735886;178735885;178735884 | chr2:179600613;179600612;179600611 |
| N2A | 3610 | 11053;11054;11055 | chr2:178735886;178735885;178735884 | chr2:179600613;179600612;179600611 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs1196213888  |
-1.755 | 0.942 | D | 0.731 | 0.489 | 0.651212884413 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/F | rs1196213888 |
-1.755 | 0.942 | D | 0.731 | 0.489 | 0.651212884413 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 2.41E-05 | 1.30959E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.77555E-04 |
| L/F | rs1196213888 |
-1.755 | 0.942 | D | 0.731 | 0.489 | 0.651212884413 |
Roncarati (2013)
| None |
DCM 
|
het; co-inherited with LMNA mutant p.K219T | None | None | N | WES prioritisation in single DCM family; co-segregates with severe phenotype when inherited alongside LMNA variant K219T (n = 5, 5 severe phenotype (total 16)) | None | None | None | None | None | None | None | None | None | None | None |
| L/F | rs1196213888 |
-1.755 | 0.942 | D | 0.731 | 0.489 | 0.651212884413 | gnomAD-4.0.0 | 7.68582E-06 | None | None | None | None | N | None | 1.69107E-05 | 5.08423E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 1.34005E-05 | 2.84349E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.6369 | likely_pathogenic | 0.5444 | ambiguous | -2.727 | Highly Destabilizing | 0.86 | D | 0.723 | prob.delet. | None | None | None | None | N |
| L/C | 0.6552 | likely_pathogenic | 0.5762 | pathogenic | -2.167 | Highly Destabilizing | 0.998 | D | 0.793 | deleterious | None | None | None | None | N |
| L/D | 0.9612 | likely_pathogenic | 0.9455 | pathogenic | -3.232 | Highly Destabilizing | 0.993 | D | 0.898 | deleterious | None | None | None | None | N |
| L/E | 0.867 | likely_pathogenic | 0.8128 | pathogenic | -2.927 | Highly Destabilizing | 0.993 | D | 0.896 | deleterious | None | None | None | None | N |
| L/F | 0.1717 | likely_benign | 0.1338 | benign | -1.624 | Destabilizing | 0.942 | D | 0.731 | prob.delet. | D | 0.57582613 | None | None | N |
| L/G | 0.847 | likely_pathogenic | 0.8011 | pathogenic | -3.353 | Highly Destabilizing | 0.978 | D | 0.895 | deleterious | None | None | None | None | N |
| L/H | 0.6299 | likely_pathogenic | 0.5418 | ambiguous | -2.896 | Highly Destabilizing | 0.997 | D | 0.885 | deleterious | D | 0.77731441 | None | None | N |
| L/I | 0.0916 | likely_benign | 0.0819 | benign | -0.871 | Destabilizing | 0.006 | N | 0.273 | neutral | N | 0.363429439 | None | None | N |
| L/K | 0.7142 | likely_pathogenic | 0.6465 | pathogenic | -2.176 | Highly Destabilizing | 0.978 | D | 0.877 | deleterious | None | None | None | None | N |
| L/M | 0.1574 | likely_benign | 0.1374 | benign | -0.979 | Destabilizing | 0.956 | D | 0.687 | prob.neutral | None | None | None | None | N |
| L/N | 0.824 | likely_pathogenic | 0.7739 | pathogenic | -2.752 | Highly Destabilizing | 0.993 | D | 0.905 | deleterious | None | None | None | None | N |
| L/P | 0.9307 | likely_pathogenic | 0.9162 | pathogenic | -1.476 | Destabilizing | 0.99 | D | 0.901 | deleterious | D | 0.77731441 | None | None | N |
| L/Q | 0.6071 | likely_pathogenic | 0.5303 | ambiguous | -2.465 | Highly Destabilizing | 0.993 | D | 0.904 | deleterious | None | None | None | None | N |
| L/R | 0.6098 | likely_pathogenic | 0.5252 | ambiguous | -2.115 | Highly Destabilizing | 0.99 | D | 0.886 | deleterious | D | 0.77731441 | None | None | N |
| L/S | 0.8137 | likely_pathogenic | 0.7344 | pathogenic | -3.456 | Highly Destabilizing | 0.978 | D | 0.865 | deleterious | None | None | None | None | N |
| L/T | 0.6946 | likely_pathogenic | 0.6068 | pathogenic | -2.974 | Highly Destabilizing | 0.956 | D | 0.791 | deleterious | None | None | None | None | N |
| L/V | 0.141 | likely_benign | 0.1149 | benign | -1.476 | Destabilizing | 0.247 | N | 0.399 | neutral | N | 0.508674183 | None | None | N |
| L/W | 0.4569 | ambiguous | 0.401 | ambiguous | -2.015 | Highly Destabilizing | 0.998 | D | 0.867 | deleterious | None | None | None | None | N |
| L/Y | 0.4985 | ambiguous | 0.4214 | ambiguous | -1.749 | Destabilizing | 0.978 | D | 0.792 | 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.