Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20868 | 62827;62828;62829 | chr2:178589123;178589122;178589121 | chr2:179453850;179453849;179453848 |
| N2AB | 19227 | 57904;57905;57906 | chr2:178589123;178589122;178589121 | chr2:179453850;179453849;179453848 |
| N2A | 18300 | 55123;55124;55125 | chr2:178589123;178589122;178589121 | chr2:179453850;179453849;179453848 |
| N2B | 11803 | 35632;35633;35634 | chr2:178589123;178589122;178589121 | chr2:179453850;179453849;179453848 |
| Novex-1 | 11928 | 36007;36008;36009 | chr2:178589123;178589122;178589121 | chr2:179453850;179453849;179453848 |
| Novex-2 | 11995 | 36208;36209;36210 | chr2:178589123;178589122;178589121 | chr2:179453850;179453849;179453848 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/G | None | None | 0.908 | N | 0.917 | 0.468 | 0.628315908551 | gnomAD-4.0.0 | 2.40143E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.62584E-06 | 0 | 0 |
| V/M | rs371004819  |
-1.299 | 0.83 | N | 0.854 | 0.294 | None | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| V/M | rs371004819 |
-1.299 | 0.83 | N | 0.854 | 0.294 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/M | rs371004819 |
-1.299 | 0.83 | N | 0.854 | 0.294 | None | gnomAD-4.0.0 | 1.11635E-05 | None | None | None | None | N | None | 1.3349E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44112E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7744 | likely_pathogenic | 0.7513 | pathogenic | -2.237 | Highly Destabilizing | 0.581 | D | 0.802 | deleterious | N | 0.491945561 | None | None | N |
| V/C | 0.9367 | likely_pathogenic | 0.9456 | pathogenic | -1.842 | Destabilizing | 0.993 | D | 0.883 | deleterious | None | None | None | None | N |
| V/D | 0.9978 | likely_pathogenic | 0.9968 | pathogenic | -3.251 | Highly Destabilizing | 0.929 | D | 0.925 | deleterious | None | None | None | None | N |
| V/E | 0.9933 | likely_pathogenic | 0.9908 | pathogenic | -3.006 | Highly Destabilizing | 0.908 | D | 0.914 | deleterious | N | 0.467490763 | None | None | N |
| V/F | 0.9678 | likely_pathogenic | 0.95 | pathogenic | -1.175 | Destabilizing | 0.866 | D | 0.886 | deleterious | None | None | None | None | N |
| V/G | 0.9399 | likely_pathogenic | 0.9301 | pathogenic | -2.777 | Highly Destabilizing | 0.908 | D | 0.917 | deleterious | N | 0.472263703 | None | None | N |
| V/H | 0.9989 | likely_pathogenic | 0.9985 | pathogenic | -2.61 | Highly Destabilizing | 0.993 | D | 0.935 | deleterious | None | None | None | None | N |
| V/I | 0.1529 | likely_benign | 0.1193 | benign | -0.7 | Destabilizing | 0.006 | N | 0.498 | neutral | None | None | None | None | N |
| V/K | 0.9972 | likely_pathogenic | 0.9959 | pathogenic | -1.897 | Destabilizing | 0.929 | D | 0.918 | deleterious | None | None | None | None | N |
| V/L | 0.765 | likely_pathogenic | 0.6838 | pathogenic | -0.7 | Destabilizing | 0.09 | N | 0.771 | deleterious | N | 0.467237273 | None | None | N |
| V/M | 0.86 | likely_pathogenic | 0.8025 | pathogenic | -0.912 | Destabilizing | 0.83 | D | 0.854 | deleterious | N | 0.490367958 | None | None | N |
| V/N | 0.992 | likely_pathogenic | 0.9889 | pathogenic | -2.33 | Highly Destabilizing | 0.976 | D | 0.943 | deleterious | None | None | None | None | N |
| V/P | 0.4796 | ambiguous | 0.4713 | ambiguous | -1.19 | Destabilizing | 0.976 | D | 0.922 | deleterious | None | None | None | None | N |
| V/Q | 0.9944 | likely_pathogenic | 0.9926 | pathogenic | -2.112 | Highly Destabilizing | 0.976 | D | 0.944 | deleterious | None | None | None | None | N |
| V/R | 0.9941 | likely_pathogenic | 0.9921 | pathogenic | -1.776 | Destabilizing | 0.929 | D | 0.942 | deleterious | None | None | None | None | N |
| V/S | 0.9539 | likely_pathogenic | 0.9448 | pathogenic | -2.856 | Highly Destabilizing | 0.929 | D | 0.911 | deleterious | None | None | None | None | N |
| V/T | 0.8886 | likely_pathogenic | 0.8743 | pathogenic | -2.48 | Highly Destabilizing | 0.648 | D | 0.837 | deleterious | None | None | None | None | N |
| V/W | 0.9996 | likely_pathogenic | 0.9994 | pathogenic | -1.808 | Destabilizing | 0.993 | D | 0.928 | deleterious | None | None | None | None | N |
| V/Y | 0.9981 | likely_pathogenic | 0.9967 | pathogenic | -1.467 | Destabilizing | 0.929 | D | 0.881 | 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.