Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25341 | 76246;76247;76248 | chr2:178570111;178570110;178570109 | chr2:179434838;179434837;179434836 |
| N2AB | 23700 | 71323;71324;71325 | chr2:178570111;178570110;178570109 | chr2:179434838;179434837;179434836 |
| N2A | 22773 | 68542;68543;68544 | chr2:178570111;178570110;178570109 | chr2:179434838;179434837;179434836 |
| N2B | 16276 | 49051;49052;49053 | chr2:178570111;178570110;178570109 | chr2:179434838;179434837;179434836 |
| Novex-1 | 16401 | 49426;49427;49428 | chr2:178570111;178570110;178570109 | chr2:179434838;179434837;179434836 |
| Novex-2 | 16468 | 49627;49628;49629 | chr2:178570111;178570110;178570109 | chr2:179434838;179434837;179434836 |
| 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/P | None | None | 0.999 | N | 0.872 | 0.645 | 0.703937047953 | gnomAD-4.0.0 | 1.59189E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85941E-06 | 0 | 0 |
| L/V | rs576067412  |
-2.124 | 0.198 | N | 0.309 | 0.098 | 0.29527378943 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/V | rs576067412 |
-2.124 | 0.198 | N | 0.309 | 0.098 | 0.29527378943 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | rs576067412 |
-2.124 | 0.198 | N | 0.309 | 0.098 | 0.29527378943 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| L/V | rs576067412 |
-2.124 | 0.198 | N | 0.309 | 0.098 | 0.29527378943 | gnomAD-4.0.0 | 2.56327E-06 | None | None | None | None | N | None | 3.38066E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.7507 | likely_pathogenic | 0.7135 | pathogenic | -3.028 | Highly Destabilizing | 0.983 | D | 0.675 | neutral | None | None | None | None | N |
| L/C | 0.8773 | likely_pathogenic | 0.865 | pathogenic | -2.001 | Highly Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| L/D | 0.9996 | likely_pathogenic | 0.9996 | pathogenic | -3.708 | Highly Destabilizing | 0.999 | D | 0.869 | deleterious | None | None | None | None | N |
| L/E | 0.9961 | likely_pathogenic | 0.9954 | pathogenic | -3.384 | Highly Destabilizing | 0.999 | D | 0.853 | deleterious | None | None | None | None | N |
| L/F | 0.8993 | likely_pathogenic | 0.8709 | pathogenic | -1.826 | Destabilizing | 0.997 | D | 0.64 | neutral | N | 0.510787434 | None | None | N |
| L/G | 0.9833 | likely_pathogenic | 0.979 | pathogenic | -3.612 | Highly Destabilizing | 0.999 | D | 0.848 | deleterious | None | None | None | None | N |
| L/H | 0.9958 | likely_pathogenic | 0.9943 | pathogenic | -3.192 | Highly Destabilizing | 1.0 | D | 0.824 | deleterious | D | 0.522397229 | None | None | N |
| L/I | 0.1095 | likely_benign | 0.1134 | benign | -1.244 | Destabilizing | 0.9 | D | 0.571 | neutral | N | 0.417138372 | None | None | N |
| L/K | 0.9958 | likely_pathogenic | 0.9953 | pathogenic | -2.44 | Highly Destabilizing | 0.999 | D | 0.824 | deleterious | None | None | None | None | N |
| L/M | 0.3877 | ambiguous | 0.3795 | ambiguous | -1.346 | Destabilizing | 0.998 | D | 0.62 | neutral | None | None | None | None | N |
| L/N | 0.9975 | likely_pathogenic | 0.9969 | pathogenic | -3.213 | Highly Destabilizing | 0.999 | D | 0.867 | deleterious | None | None | None | None | N |
| L/P | 0.9874 | likely_pathogenic | 0.984 | pathogenic | -1.834 | Destabilizing | 0.999 | D | 0.872 | deleterious | N | 0.499520034 | None | None | N |
| L/Q | 0.9876 | likely_pathogenic | 0.9847 | pathogenic | -2.843 | Highly Destabilizing | 0.999 | D | 0.852 | deleterious | None | None | None | None | N |
| L/R | 0.9903 | likely_pathogenic | 0.9877 | pathogenic | -2.486 | Highly Destabilizing | 0.999 | D | 0.853 | deleterious | D | 0.522397229 | None | None | N |
| L/S | 0.9852 | likely_pathogenic | 0.9799 | pathogenic | -3.686 | Highly Destabilizing | 0.998 | D | 0.796 | deleterious | None | None | None | None | N |
| L/T | 0.8451 | likely_pathogenic | 0.825 | pathogenic | -3.204 | Highly Destabilizing | 0.983 | D | 0.675 | neutral | None | None | None | None | N |
| L/V | 0.0786 | likely_benign | 0.0801 | benign | -1.834 | Destabilizing | 0.198 | N | 0.309 | neutral | N | 0.380673352 | None | None | N |
| L/W | 0.9933 | likely_pathogenic | 0.9902 | pathogenic | -2.126 | Highly Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| L/Y | 0.9936 | likely_pathogenic | 0.9915 | pathogenic | -2.025 | Highly Destabilizing | 0.999 | D | 0.726 | prob.delet. | 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.