Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28908 | 86947;86948;86949 | chr2:178559410;178559409;178559408 | chr2:179424137;179424136;179424135 |
| N2AB | 27267 | 82024;82025;82026 | chr2:178559410;178559409;178559408 | chr2:179424137;179424136;179424135 |
| N2A | 26340 | 79243;79244;79245 | chr2:178559410;178559409;178559408 | chr2:179424137;179424136;179424135 |
| N2B | 19843 | 59752;59753;59754 | chr2:178559410;178559409;178559408 | chr2:179424137;179424136;179424135 |
| Novex-1 | 19968 | 60127;60128;60129 | chr2:178559410;178559409;178559408 | chr2:179424137;179424136;179424135 |
| Novex-2 | 20035 | 60328;60329;60330 | chr2:178559410;178559409;178559408 | chr2:179424137;179424136;179424135 |
| 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 | rs377612718  |
0.243 | 0.896 | N | 0.451 | 0.1 | None | gnomAD-2.1.1 | 1.06992E-04 | None | None | None | None | N | None | 2.89232E-04 | 4.80633E-04 | None | 0 | 0 | None | 0 | None | 0 | 4.68E-05 | 0 |
| N/S | rs377612718 |
0.243 | 0.896 | N | 0.451 | 0.1 | None | gnomAD-3.1.2 | 1.90516E-04 | None | None | None | None | N | None | 3.8584E-04 | 5.89545E-04 | 0 | 0 | 1.9253E-04 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| N/S | rs377612718 |
0.243 | 0.896 | N | 0.451 | 0.1 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| N/S | rs377612718 |
0.243 | 0.896 | N | 0.451 | 0.1 | None | gnomAD-4.0.0 | 6.87824E-05 | None | None | None | None | N | None | 2.9313E-04 | 4.49955E-04 | None | 0 | 6.68568E-05 | None | 0 | 0 | 4.83166E-05 | 0 | 3.20102E-05 |
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 | 0.1324 | likely_benign | 0.117 | benign | -0.11 | Destabilizing | 0.851 | D | 0.434 | neutral | None | None | None | None | N |
| N/C | 0.2079 | likely_benign | 0.1806 | benign | 0.233 | Stabilizing | 0.999 | D | 0.673 | neutral | None | None | None | None | N |
| N/D | 0.0922 | likely_benign | 0.0969 | benign | 0.163 | Stabilizing | 0.011 | N | 0.144 | neutral | N | 0.448154712 | None | None | N |
| N/E | 0.2775 | likely_benign | 0.2752 | benign | 0.103 | Stabilizing | 0.851 | D | 0.419 | neutral | None | None | None | None | N |
| N/F | 0.427 | ambiguous | 0.3881 | ambiguous | -0.673 | Destabilizing | 0.996 | D | 0.613 | neutral | None | None | None | None | N |
| N/G | 0.1403 | likely_benign | 0.1235 | benign | -0.215 | Destabilizing | 0.034 | N | 0.162 | neutral | None | None | None | None | N |
| N/H | 0.0927 | likely_benign | 0.0898 | benign | -0.221 | Destabilizing | 0.995 | D | 0.481 | neutral | N | 0.484522289 | None | None | N |
| N/I | 0.2422 | likely_benign | 0.2168 | benign | 0.068 | Stabilizing | 0.995 | D | 0.613 | neutral | N | 0.497146042 | None | None | N |
| N/K | 0.2614 | likely_benign | 0.2596 | benign | 0.169 | Stabilizing | 0.946 | D | 0.429 | neutral | N | 0.496103374 | None | None | N |
| N/L | 0.2095 | likely_benign | 0.1909 | benign | 0.068 | Stabilizing | 0.988 | D | 0.585 | neutral | None | None | None | None | N |
| N/M | 0.2943 | likely_benign | 0.2601 | benign | 0.173 | Stabilizing | 0.999 | D | 0.563 | neutral | None | None | None | None | N |
| N/P | 0.4946 | ambiguous | 0.447 | ambiguous | 0.032 | Stabilizing | 0.996 | D | 0.553 | neutral | None | None | None | None | N |
| N/Q | 0.2416 | likely_benign | 0.2321 | benign | -0.194 | Destabilizing | 0.988 | D | 0.45 | neutral | None | None | None | None | N |
| N/R | 0.3001 | likely_benign | 0.2971 | benign | 0.242 | Stabilizing | 0.988 | D | 0.448 | neutral | None | None | None | None | N |
| N/S | 0.0691 | likely_benign | 0.0636 | benign | 0.022 | Stabilizing | 0.896 | D | 0.451 | neutral | N | 0.513168983 | None | None | N |
| N/T | 0.1196 | likely_benign | 0.1058 | benign | 0.08 | Stabilizing | 0.946 | D | 0.43 | neutral | N | 0.478027829 | None | None | N |
| N/V | 0.1983 | likely_benign | 0.1851 | benign | 0.032 | Stabilizing | 0.988 | D | 0.595 | neutral | None | None | None | None | N |
| N/W | 0.6891 | likely_pathogenic | 0.6591 | pathogenic | -0.779 | Destabilizing | 0.999 | D | 0.714 | prob.delet. | None | None | None | None | N |
| N/Y | 0.1565 | likely_benign | 0.1458 | benign | -0.459 | Destabilizing | 0.995 | D | 0.551 | neutral | N | 0.496892552 | 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.