Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30217 | 90874;90875;90876 | chr2:178552251;178552250;178552249 | chr2:179416978;179416977;179416976 |
| N2AB | 28576 | 85951;85952;85953 | chr2:178552251;178552250;178552249 | chr2:179416978;179416977;179416976 |
| N2A | 27649 | 83170;83171;83172 | chr2:178552251;178552250;178552249 | chr2:179416978;179416977;179416976 |
| N2B | 21152 | 63679;63680;63681 | chr2:178552251;178552250;178552249 | chr2:179416978;179416977;179416976 |
| Novex-1 | 21277 | 64054;64055;64056 | chr2:178552251;178552250;178552249 | chr2:179416978;179416977;179416976 |
| Novex-2 | 21344 | 64255;64256;64257 | chr2:178552251;178552250;178552249 | chr2:179416978;179416977;179416976 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs776252505  |
-2.522 | 0.722 | N | 0.623 | 0.392 | 0.516770950016 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| I/T | rs776252505 |
-2.522 | 0.722 | N | 0.623 | 0.392 | 0.516770950016 | gnomAD-4.0.0 | 4.77584E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71834E-06 | 1.43427E-05 | 0 |
| I/V | rs1184438551 |
None | 0.008 | N | 0.221 | 0.05 | 0.299770980665 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs1184438551 |
None | 0.008 | N | 0.221 | 0.05 | 0.299770980665 | gnomAD-4.0.0 | 2.43595E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.89184E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8731 | likely_pathogenic | 0.8581 | pathogenic | -2.813 | Highly Destabilizing | 0.633 | D | 0.564 | neutral | None | None | None | None | I |
| I/C | 0.8938 | likely_pathogenic | 0.8807 | pathogenic | -2.245 | Highly Destabilizing | 0.996 | D | 0.701 | prob.neutral | None | None | None | None | I |
| I/D | 0.998 | likely_pathogenic | 0.9971 | pathogenic | -3.357 | Highly Destabilizing | 0.987 | D | 0.734 | prob.delet. | None | None | None | None | I |
| I/E | 0.9934 | likely_pathogenic | 0.9898 | pathogenic | -3.053 | Highly Destabilizing | 0.961 | D | 0.722 | prob.delet. | None | None | None | None | I |
| I/F | 0.289 | likely_benign | 0.2488 | benign | -1.717 | Destabilizing | 0.018 | N | 0.345 | neutral | N | 0.466212272 | None | None | I |
| I/G | 0.9859 | likely_pathogenic | 0.9809 | pathogenic | -3.437 | Highly Destabilizing | 0.961 | D | 0.712 | prob.delet. | None | None | None | None | I |
| I/H | 0.9843 | likely_pathogenic | 0.9781 | pathogenic | -3.001 | Highly Destabilizing | 0.996 | D | 0.745 | deleterious | None | None | None | None | I |
| I/K | 0.9853 | likely_pathogenic | 0.9752 | pathogenic | -2.435 | Highly Destabilizing | 0.961 | D | 0.721 | prob.delet. | None | None | None | None | I |
| I/L | 0.1594 | likely_benign | 0.1575 | benign | -0.966 | Destabilizing | 0.19 | N | 0.391 | neutral | N | 0.476314387 | None | None | I |
| I/M | 0.1924 | likely_benign | 0.1851 | benign | -0.999 | Destabilizing | 0.901 | D | 0.649 | neutral | N | 0.479761078 | None | None | I |
| I/N | 0.9758 | likely_pathogenic | 0.9638 | pathogenic | -3.039 | Highly Destabilizing | 0.983 | D | 0.747 | deleterious | N | 0.480268057 | None | None | I |
| I/P | 0.9958 | likely_pathogenic | 0.995 | pathogenic | -1.567 | Destabilizing | 0.987 | D | 0.749 | deleterious | None | None | None | None | I |
| I/Q | 0.9822 | likely_pathogenic | 0.9738 | pathogenic | -2.742 | Highly Destabilizing | 0.987 | D | 0.745 | deleterious | None | None | None | None | I |
| I/R | 0.9774 | likely_pathogenic | 0.9653 | pathogenic | -2.315 | Highly Destabilizing | 0.961 | D | 0.753 | deleterious | None | None | None | None | I |
| I/S | 0.9598 | likely_pathogenic | 0.949 | pathogenic | -3.723 | Highly Destabilizing | 0.901 | D | 0.665 | neutral | N | 0.467733209 | None | None | I |
| I/T | 0.9158 | likely_pathogenic | 0.8974 | pathogenic | -3.244 | Highly Destabilizing | 0.722 | D | 0.623 | neutral | N | 0.466972741 | None | None | I |
| I/V | 0.0818 | likely_benign | 0.0859 | benign | -1.567 | Destabilizing | 0.008 | N | 0.221 | neutral | N | 0.479237262 | None | None | I |
| I/W | 0.9781 | likely_pathogenic | 0.9705 | pathogenic | -2.137 | Highly Destabilizing | 0.996 | D | 0.745 | deleterious | None | None | None | None | I |
| I/Y | 0.9067 | likely_pathogenic | 0.8684 | pathogenic | -1.866 | Destabilizing | 0.858 | D | 0.679 | prob.neutral | None | None | None | None | I |
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.