Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28645 | 86158;86159;86160 | chr2:178560199;178560198;178560197 | chr2:179424926;179424925;179424924 |
| N2AB | 27004 | 81235;81236;81237 | chr2:178560199;178560198;178560197 | chr2:179424926;179424925;179424924 |
| N2A | 26077 | 78454;78455;78456 | chr2:178560199;178560198;178560197 | chr2:179424926;179424925;179424924 |
| N2B | 19580 | 58963;58964;58965 | chr2:178560199;178560198;178560197 | chr2:179424926;179424925;179424924 |
| Novex-1 | 19705 | 59338;59339;59340 | chr2:178560199;178560198;178560197 | chr2:179424926;179424925;179424924 |
| Novex-2 | 19772 | 59539;59540;59541 | chr2:178560199;178560198;178560197 | chr2:179424926;179424925;179424924 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/E | None | None | 1.0 | N | 0.807 | 0.384 | 0.534191878353 | gnomAD-4.0.0 | 6.84201E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99462E-07 | 0 | 0 |
| A/T | rs879226652  |
-2.117 | 1.0 | N | 0.769 | 0.251 | 0.241078983079 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11433E-04 | None | 0 | None | 0 | 0 | 0 |
| A/T | rs879226652 |
-2.117 | 1.0 | N | 0.769 | 0.251 | 0.241078983079 | gnomAD-4.0.0 | 3.18249E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.54785E-05 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs375603504 |
-0.83 | 0.999 | N | 0.675 | 0.295 | None | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 1.40371E-04 |
| A/V | rs375603504 |
-0.83 | 0.999 | N | 0.675 | 0.295 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| A/V | rs375603504 |
-0.83 | 0.999 | N | 0.675 | 0.295 | None | gnomAD-4.0.0 | 9.91526E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.27141E-05 | 0 | 1.60102E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6391 | likely_pathogenic | 0.6649 | pathogenic | -1.882 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| A/D | 0.9936 | likely_pathogenic | 0.996 | pathogenic | -3.112 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| A/E | 0.9815 | likely_pathogenic | 0.988 | pathogenic | -2.953 | Highly Destabilizing | 1.0 | D | 0.807 | deleterious | N | 0.501039474 | None | None | N |
| A/F | 0.9674 | likely_pathogenic | 0.9697 | pathogenic | -0.872 | Destabilizing | 1.0 | D | 0.822 | deleterious | None | None | None | None | N |
| A/G | 0.4896 | ambiguous | 0.4725 | ambiguous | -1.819 | Destabilizing | 0.999 | D | 0.583 | neutral | N | 0.486151223 | None | None | N |
| A/H | 0.9922 | likely_pathogenic | 0.9947 | pathogenic | -1.826 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| A/I | 0.7474 | likely_pathogenic | 0.7741 | pathogenic | -0.431 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| A/K | 0.9949 | likely_pathogenic | 0.9969 | pathogenic | -1.483 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| A/L | 0.6832 | likely_pathogenic | 0.7125 | pathogenic | -0.431 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| A/M | 0.7207 | likely_pathogenic | 0.7383 | pathogenic | -0.915 | Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| A/N | 0.9718 | likely_pathogenic | 0.9794 | pathogenic | -1.859 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| A/P | 0.79 | likely_pathogenic | 0.778 | pathogenic | -0.73 | Destabilizing | 1.0 | D | 0.821 | deleterious | N | 0.471690591 | None | None | N |
| A/Q | 0.9726 | likely_pathogenic | 0.9795 | pathogenic | -1.767 | Destabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | N |
| A/R | 0.9851 | likely_pathogenic | 0.9902 | pathogenic | -1.387 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| A/S | 0.3372 | likely_benign | 0.3464 | ambiguous | -2.159 | Highly Destabilizing | 0.999 | D | 0.617 | neutral | N | 0.484162986 | None | None | N |
| A/T | 0.5015 | ambiguous | 0.534 | ambiguous | -1.903 | Destabilizing | 1.0 | D | 0.769 | deleterious | N | 0.495543227 | None | None | N |
| A/V | 0.4501 | ambiguous | 0.4813 | ambiguous | -0.73 | Destabilizing | 0.999 | D | 0.675 | prob.neutral | N | 0.507491017 | None | None | N |
| A/W | 0.9956 | likely_pathogenic | 0.997 | pathogenic | -1.493 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| A/Y | 0.9869 | likely_pathogenic | 0.9897 | pathogenic | -1.086 | Destabilizing | 1.0 | D | 0.851 | 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.