Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23843 | 71752;71753;71754 | chr2:178574605;178574604;178574603 | chr2:179439332;179439331;179439330 |
| N2AB | 22202 | 66829;66830;66831 | chr2:178574605;178574604;178574603 | chr2:179439332;179439331;179439330 |
| N2A | 21275 | 64048;64049;64050 | chr2:178574605;178574604;178574603 | chr2:179439332;179439331;179439330 |
| N2B | 14778 | 44557;44558;44559 | chr2:178574605;178574604;178574603 | chr2:179439332;179439331;179439330 |
| Novex-1 | 14903 | 44932;44933;44934 | chr2:178574605;178574604;178574603 | chr2:179439332;179439331;179439330 |
| Novex-2 | 14970 | 45133;45134;45135 | chr2:178574605;178574604;178574603 | chr2:179439332;179439331;179439330 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | None | None | None | N | 0.295 | 0.053 | 0.255270683199 | gnomAD-4.0.0 | 1.36884E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79933E-06 | 0 | 0 |
| M/R | None | None | 0.484 | N | 0.818 | 0.466 | 0.616224366892 | gnomAD-4.0.0 | 1.59228E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77793E-05 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs757085121  |
-1.631 | 0.117 | N | 0.759 | 0.438 | 0.625156528392 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| M/T | rs757085121 |
-1.631 | 0.117 | N | 0.759 | 0.438 | 0.625156528392 | gnomAD-4.0.0 | 3.18456E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71994E-06 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.7314 | likely_pathogenic | 0.6372 | pathogenic | -1.822 | Destabilizing | 0.067 | N | 0.68 | prob.neutral | None | None | None | None | N |
| M/C | 0.8327 | likely_pathogenic | 0.7939 | pathogenic | -2.594 | Highly Destabilizing | 0.935 | D | 0.783 | deleterious | None | None | None | None | N |
| M/D | 0.9983 | likely_pathogenic | 0.9958 | pathogenic | -2.005 | Highly Destabilizing | 0.555 | D | 0.809 | deleterious | None | None | None | None | N |
| M/E | 0.9784 | likely_pathogenic | 0.96 | pathogenic | -1.792 | Destabilizing | 0.555 | D | 0.797 | deleterious | None | None | None | None | N |
| M/F | 0.717 | likely_pathogenic | 0.6671 | pathogenic | -0.6 | Destabilizing | 0.149 | N | 0.683 | prob.neutral | None | None | None | None | N |
| M/G | 0.9687 | likely_pathogenic | 0.9394 | pathogenic | -2.271 | Highly Destabilizing | 0.262 | N | 0.779 | deleterious | None | None | None | None | N |
| M/H | 0.9862 | likely_pathogenic | 0.9729 | pathogenic | -2.019 | Highly Destabilizing | 0.935 | D | 0.765 | deleterious | None | None | None | None | N |
| M/I | 0.4009 | ambiguous | 0.3059 | benign | -0.553 | Destabilizing | None | N | 0.295 | neutral | N | 0.440324662 | None | None | N |
| M/K | 0.9492 | likely_pathogenic | 0.9004 | pathogenic | -1.118 | Destabilizing | 0.211 | N | 0.785 | deleterious | N | 0.514427376 | None | None | N |
| M/L | 0.3335 | likely_benign | 0.2526 | benign | -0.553 | Destabilizing | 0.002 | N | 0.466 | neutral | N | 0.473066225 | None | None | N |
| M/N | 0.979 | likely_pathogenic | 0.958 | pathogenic | -1.515 | Destabilizing | 0.791 | D | 0.806 | deleterious | None | None | None | None | N |
| M/P | 0.9986 | likely_pathogenic | 0.9969 | pathogenic | -0.956 | Destabilizing | 0.791 | D | 0.804 | deleterious | None | None | None | None | N |
| M/Q | 0.8605 | likely_pathogenic | 0.7914 | pathogenic | -1.24 | Destabilizing | 0.791 | D | 0.694 | prob.neutral | None | None | None | None | N |
| M/R | 0.9509 | likely_pathogenic | 0.9006 | pathogenic | -1.306 | Destabilizing | 0.484 | N | 0.818 | deleterious | N | 0.503071071 | None | None | N |
| M/S | 0.9032 | likely_pathogenic | 0.8429 | pathogenic | -2.046 | Highly Destabilizing | 0.262 | N | 0.762 | deleterious | None | None | None | None | N |
| M/T | 0.8474 | likely_pathogenic | 0.7592 | pathogenic | -1.7 | Destabilizing | 0.117 | N | 0.759 | deleterious | N | 0.495816142 | None | None | N |
| M/V | 0.1279 | likely_benign | 0.1059 | benign | -0.956 | Destabilizing | 0.004 | N | 0.467 | neutral | N | 0.405441298 | None | None | N |
| M/W | 0.9886 | likely_pathogenic | 0.9731 | pathogenic | -0.933 | Destabilizing | 0.935 | D | 0.758 | deleterious | None | None | None | None | N |
| M/Y | 0.971 | likely_pathogenic | 0.9498 | pathogenic | -0.811 | Destabilizing | 0.555 | D | 0.817 | 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.