Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15791 | 47596;47597;47598 | chr2:178617980;178617979;178617978 | chr2:179482707;179482706;179482705 |
| N2AB | 14150 | 42673;42674;42675 | chr2:178617980;178617979;178617978 | chr2:179482707;179482706;179482705 |
| N2A | 13223 | 39892;39893;39894 | chr2:178617980;178617979;178617978 | chr2:179482707;179482706;179482705 |
| N2B | 6726 | 20401;20402;20403 | chr2:178617980;178617979;178617978 | chr2:179482707;179482706;179482705 |
| Novex-1 | 6851 | 20776;20777;20778 | chr2:178617980;178617979;178617978 | chr2:179482707;179482706;179482705 |
| Novex-2 | 6918 | 20977;20978;20979 | chr2:178617980;178617979;178617978 | chr2:179482707;179482706;179482705 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs540588062  |
0.007 | 1.0 | N | 0.799 | 0.42 | 0.61225159808 | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 2.28773E-04 | None | 0 | 0 | 1.65837E-04 |
| T/I | rs540588062 |
0.007 | 1.0 | N | 0.799 | 0.42 | 0.61225159808 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| T/I | rs540588062 |
0.007 | 1.0 | N | 0.799 | 0.42 | 0.61225159808 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| T/I | rs540588062 |
0.007 | 1.0 | N | 0.799 | 0.42 | 0.61225159808 | gnomAD-4.0.0 | 7.44133E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.48104E-07 | 9.88446E-05 | 3.20431E-05 |
| T/P | rs1269031927 |
-0.337 | 1.0 | D | 0.786 | 0.574 | 0.665027746237 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| T/P | rs1269031927 |
-0.337 | 1.0 | D | 0.786 | 0.574 | 0.665027746237 | gnomAD-4.0.0 | 1.59348E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86257E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1343 | likely_benign | 0.125 | benign | -0.525 | Destabilizing | 0.999 | D | 0.484 | neutral | D | 0.624106923 | None | None | I |
| T/C | 0.5861 | likely_pathogenic | 0.5005 | ambiguous | -0.223 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| T/D | 0.5224 | ambiguous | 0.4638 | ambiguous | -0.379 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | I |
| T/E | 0.324 | likely_benign | 0.2927 | benign | -0.447 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | I |
| T/F | 0.4199 | ambiguous | 0.3576 | ambiguous | -0.917 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | I |
| T/G | 0.332 | likely_benign | 0.2943 | benign | -0.692 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | I |
| T/H | 0.4237 | ambiguous | 0.3821 | ambiguous | -1.063 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | I |
| T/I | 0.2329 | likely_benign | 0.2046 | benign | -0.193 | Destabilizing | 1.0 | D | 0.799 | deleterious | N | 0.518255549 | None | None | I |
| T/K | 0.2762 | likely_benign | 0.2819 | benign | -0.572 | Destabilizing | 1.0 | D | 0.787 | deleterious | N | 0.513093926 | None | None | I |
| T/L | 0.131 | likely_benign | 0.1189 | benign | -0.193 | Destabilizing | 0.999 | D | 0.666 | neutral | None | None | None | None | I |
| T/M | 0.1297 | likely_benign | 0.1177 | benign | 0.25 | Stabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | I |
| T/N | 0.209 | likely_benign | 0.1801 | benign | -0.369 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | I |
| T/P | 0.6075 | likely_pathogenic | 0.6282 | pathogenic | -0.275 | Destabilizing | 1.0 | D | 0.786 | deleterious | D | 0.746557063 | None | None | I |
| T/Q | 0.2516 | likely_benign | 0.2431 | benign | -0.688 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | I |
| T/R | 0.2405 | likely_benign | 0.2431 | benign | -0.205 | Destabilizing | 1.0 | D | 0.802 | deleterious | D | 0.599686093 | None | None | I |
| T/S | 0.1547 | likely_benign | 0.1349 | benign | -0.548 | Destabilizing | 0.999 | D | 0.487 | neutral | N | 0.520710606 | None | None | I |
| T/V | 0.1854 | likely_benign | 0.1613 | benign | -0.275 | Destabilizing | 0.999 | D | 0.581 | neutral | None | None | None | None | I |
| T/W | 0.7373 | likely_pathogenic | 0.6747 | pathogenic | -0.877 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | I |
| T/Y | 0.492 | ambiguous | 0.4321 | ambiguous | -0.625 | Destabilizing | 1.0 | D | 0.827 | deleterious | 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.