Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27733 | 83422;83423;83424 | chr2:178562935;178562934;178562933 | chr2:179427662;179427661;179427660 |
| N2AB | 26092 | 78499;78500;78501 | chr2:178562935;178562934;178562933 | chr2:179427662;179427661;179427660 |
| N2A | 25165 | 75718;75719;75720 | chr2:178562935;178562934;178562933 | chr2:179427662;179427661;179427660 |
| N2B | 18668 | 56227;56228;56229 | chr2:178562935;178562934;178562933 | chr2:179427662;179427661;179427660 |
| Novex-1 | 18793 | 56602;56603;56604 | chr2:178562935;178562934;178562933 | chr2:179427662;179427661;179427660 |
| Novex-2 | 18860 | 56803;56804;56805 | chr2:178562935;178562934;178562933 | chr2:179427662;179427661;179427660 |
| 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/F | rs1393748586  |
-1.622 | 0.998 | D | 0.713 | 0.76 | 0.835424349326 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65782E-04 |
| I/F | rs1393748586 |
-1.622 | 0.998 | D | 0.713 | 0.76 | 0.835424349326 | gnomAD-4.0.0 | 1.59169E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02517E-05 |
| I/L | None | None | 0.889 | D | 0.479 | 0.606 | 0.760994400293 | gnomAD-4.0.0 | 1.59169E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02517E-05 |
| I/T | rs759928014 |
-1.753 | 0.989 | D | 0.757 | 0.807 | 0.891955713682 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | I | None | 0 | 5.81E-05 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 8.9E-06 | 0 |
| I/T | rs759928014 |
-1.753 | 0.989 | D | 0.757 | 0.807 | 0.891955713682 | gnomAD-4.0.0 | 3.48986E-05 | None | None | None | None | I | None | 0 | 6.71081E-05 | None | 0 | 0 | None | 0 | 0 | 4.04775E-05 | 3.4781E-05 | 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 | 0.7482 | likely_pathogenic | 0.7242 | pathogenic | -2.744 | Highly Destabilizing | 0.992 | D | 0.675 | neutral | None | None | None | None | I |
| I/C | 0.9113 | likely_pathogenic | 0.8995 | pathogenic | -2.319 | Highly Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| I/D | 0.9933 | likely_pathogenic | 0.9927 | pathogenic | -3.45 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | I |
| I/E | 0.9772 | likely_pathogenic | 0.9757 | pathogenic | -3.275 | Highly Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | I |
| I/F | 0.6127 | likely_pathogenic | 0.596 | pathogenic | -1.633 | Destabilizing | 0.998 | D | 0.713 | prob.delet. | D | 0.621011426 | None | None | I |
| I/G | 0.9801 | likely_pathogenic | 0.9779 | pathogenic | -3.234 | Highly Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | I |
| I/H | 0.9744 | likely_pathogenic | 0.9714 | pathogenic | -2.59 | Highly Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | I |
| I/K | 0.9517 | likely_pathogenic | 0.9482 | pathogenic | -2.24 | Highly Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | I |
| I/L | 0.195 | likely_benign | 0.1739 | benign | -1.333 | Destabilizing | 0.889 | D | 0.479 | neutral | D | 0.573249114 | None | None | I |
| I/M | 0.1718 | likely_benign | 0.1636 | benign | -1.408 | Destabilizing | 0.998 | D | 0.682 | prob.neutral | D | 0.604588456 | None | None | I |
| I/N | 0.9246 | likely_pathogenic | 0.9173 | pathogenic | -2.54 | Highly Destabilizing | 0.999 | D | 0.823 | deleterious | D | 0.622020447 | None | None | I |
| I/P | 0.9922 | likely_pathogenic | 0.9922 | pathogenic | -1.785 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | I |
| I/Q | 0.9564 | likely_pathogenic | 0.953 | pathogenic | -2.491 | Highly Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | I |
| I/R | 0.9311 | likely_pathogenic | 0.9275 | pathogenic | -1.782 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | I |
| I/S | 0.8488 | likely_pathogenic | 0.8362 | pathogenic | -3.155 | Highly Destabilizing | 0.998 | D | 0.811 | deleterious | D | 0.622020447 | None | None | I |
| I/T | 0.4989 | ambiguous | 0.449 | ambiguous | -2.851 | Highly Destabilizing | 0.989 | D | 0.757 | deleterious | D | 0.637636199 | None | None | I |
| I/V | 0.1128 | likely_benign | 0.104 | benign | -1.785 | Destabilizing | 0.333 | N | 0.282 | neutral | D | 0.542889358 | None | None | I |
| I/W | 0.978 | likely_pathogenic | 0.9754 | pathogenic | -2.022 | Highly Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | I |
| I/Y | 0.9472 | likely_pathogenic | 0.9443 | pathogenic | -1.816 | Destabilizing | 1.0 | D | 0.741 | 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.