Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20441 | 61546;61547;61548 | chr2:178590404;178590403;178590402 | chr2:179455131;179455130;179455129 |
| N2AB | 18800 | 56623;56624;56625 | chr2:178590404;178590403;178590402 | chr2:179455131;179455130;179455129 |
| N2A | 17873 | 53842;53843;53844 | chr2:178590404;178590403;178590402 | chr2:179455131;179455130;179455129 |
| N2B | 11376 | 34351;34352;34353 | chr2:178590404;178590403;178590402 | chr2:179455131;179455130;179455129 |
| Novex-1 | 11501 | 34726;34727;34728 | chr2:178590404;178590403;178590402 | chr2:179455131;179455130;179455129 |
| Novex-2 | 11568 | 34927;34928;34929 | chr2:178590404;178590403;178590402 | chr2:179455131;179455130;179455129 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs147580753  |
-0.921 | 0.101 | N | 0.327 | 0.126 | None | gnomAD-2.1.1 | 3.54981E-04 | None | None | None | None | N | None | 3.69141E-03 | 1.73661E-04 | None | 0 | 0 | None | 0 | None | 0 | 1.59E-05 | 0 |
| N/S | rs147580753 |
-0.921 | 0.101 | N | 0.327 | 0.126 | None | gnomAD-3.1.2 | 1.08494E-03 | None | None | None | None | N | None | 3.90889E-03 | 1.96618E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | rs147580753 |
-0.921 | 0.101 | N | 0.327 | 0.126 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 1.5E-03 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| N/S | rs147580753 |
-0.921 | 0.101 | N | 0.327 | 0.126 | None | gnomAD-4.0.0 | 1.94152E-04 | None | None | None | None | N | None | 3.87628E-03 | 1.68577E-04 | None | 3.44021E-05 | 0 | None | 0 | 0 | 8.49574E-07 | 1.12042E-05 | 1.44755E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.1817 | likely_benign | 0.1943 | benign | -0.909 | Destabilizing | 0.004 | N | 0.167 | neutral | None | None | None | None | N |
| N/C | 0.1845 | likely_benign | 0.2109 | benign | -0.053 | Destabilizing | 0.983 | D | 0.472 | neutral | None | None | None | None | N |
| N/D | 0.1888 | likely_benign | 0.1541 | benign | -0.495 | Destabilizing | 0.351 | N | 0.321 | neutral | N | 0.458547851 | None | None | N |
| N/E | 0.2931 | likely_benign | 0.2631 | benign | -0.34 | Destabilizing | 0.418 | N | 0.281 | neutral | None | None | None | None | N |
| N/F | 0.4567 | ambiguous | 0.4909 | ambiguous | -0.51 | Destabilizing | 0.836 | D | 0.504 | neutral | None | None | None | None | N |
| N/G | 0.306 | likely_benign | 0.3194 | benign | -1.289 | Destabilizing | 0.228 | N | 0.282 | neutral | None | None | None | None | N |
| N/H | 0.1085 | likely_benign | 0.1118 | benign | -0.824 | Destabilizing | 0.921 | D | 0.385 | neutral | N | 0.449659009 | None | None | N |
| N/I | 0.1805 | likely_benign | 0.1861 | benign | 0.082 | Stabilizing | 0.213 | N | 0.396 | neutral | N | 0.429187736 | None | None | N |
| N/K | 0.3007 | likely_benign | 0.2675 | benign | -0.199 | Destabilizing | 0.351 | N | 0.287 | neutral | N | 0.433900122 | None | None | N |
| N/L | 0.2114 | likely_benign | 0.2195 | benign | 0.082 | Stabilizing | 0.129 | N | 0.358 | neutral | None | None | None | None | N |
| N/M | 0.2209 | likely_benign | 0.2475 | benign | 0.318 | Stabilizing | 0.836 | D | 0.441 | neutral | None | None | None | None | N |
| N/P | 0.9229 | likely_pathogenic | 0.8964 | pathogenic | -0.219 | Destabilizing | 0.836 | D | 0.483 | neutral | None | None | None | None | N |
| N/Q | 0.2377 | likely_benign | 0.2423 | benign | -0.686 | Destabilizing | 0.836 | D | 0.377 | neutral | None | None | None | None | N |
| N/R | 0.3216 | likely_benign | 0.2939 | benign | -0.313 | Destabilizing | 0.418 | N | 0.401 | neutral | None | None | None | None | N |
| N/S | 0.0791 | likely_benign | 0.081 | benign | -0.967 | Destabilizing | 0.101 | N | 0.327 | neutral | N | 0.436438995 | None | None | N |
| N/T | 0.1041 | likely_benign | 0.1111 | benign | -0.606 | Destabilizing | 0.001 | N | 0.059 | neutral | N | 0.385735242 | None | None | N |
| N/V | 0.17 | likely_benign | 0.181 | benign | -0.219 | Destabilizing | 0.004 | N | 0.159 | neutral | None | None | None | None | N |
| N/W | 0.7042 | likely_pathogenic | 0.7108 | pathogenic | -0.285 | Destabilizing | 0.983 | D | 0.523 | neutral | None | None | None | None | N |
| N/Y | 0.1623 | likely_benign | 0.1542 | benign | -0.044 | Destabilizing | 0.921 | D | 0.462 | neutral | N | 0.483944941 | 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.