Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23761 | 71506;71507;71508 | chr2:178574851;178574850;178574849 | chr2:179439578;179439577;179439576 |
| N2AB | 22120 | 66583;66584;66585 | chr2:178574851;178574850;178574849 | chr2:179439578;179439577;179439576 |
| N2A | 21193 | 63802;63803;63804 | chr2:178574851;178574850;178574849 | chr2:179439578;179439577;179439576 |
| N2B | 14696 | 44311;44312;44313 | chr2:178574851;178574850;178574849 | chr2:179439578;179439577;179439576 |
| Novex-1 | 14821 | 44686;44687;44688 | chr2:178574851;178574850;178574849 | chr2:179439578;179439577;179439576 |
| Novex-2 | 14888 | 44887;44888;44889 | chr2:178574851;178574850;178574849 | chr2:179439578;179439577;179439576 |
| 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 | None | None | 0.362 | N | 0.364 | 0.121 | 0.159798565429 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| N/Y | rs1411198108  |
-0.41 | 0.999 | N | 0.841 | 0.455 | 0.419957187557 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| N/Y | rs1411198108 |
-0.41 | 0.999 | N | 0.841 | 0.455 | 0.419957187557 | gnomAD-4.0.0 | 3.18555E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86656E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.6488 | likely_pathogenic | 0.7368 | pathogenic | -1.145 | Destabilizing | 0.966 | D | 0.546 | neutral | None | None | None | None | N |
| N/C | 0.3365 | likely_benign | 0.4044 | ambiguous | -0.568 | Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| N/D | 0.743 | likely_pathogenic | 0.7974 | pathogenic | -1.715 | Destabilizing | 0.977 | D | 0.47 | neutral | N | 0.512766338 | None | None | N |
| N/E | 0.9592 | likely_pathogenic | 0.9718 | pathogenic | -1.535 | Destabilizing | 0.983 | D | 0.545 | neutral | None | None | None | None | N |
| N/F | 0.93 | likely_pathogenic | 0.9414 | pathogenic | -0.83 | Destabilizing | 0.999 | D | 0.85 | deleterious | None | None | None | None | N |
| N/G | 0.4362 | ambiguous | 0.5261 | ambiguous | -1.505 | Destabilizing | 0.966 | D | 0.478 | neutral | None | None | None | None | N |
| N/H | 0.3112 | likely_benign | 0.3951 | ambiguous | -1.047 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | N | 0.477210969 | None | None | N |
| N/I | 0.9116 | likely_pathogenic | 0.9398 | pathogenic | -0.203 | Destabilizing | 0.997 | D | 0.847 | deleterious | N | 0.472382743 | None | None | N |
| N/K | 0.9381 | likely_pathogenic | 0.9577 | pathogenic | -0.348 | Destabilizing | 0.977 | D | 0.548 | neutral | N | 0.48821461 | None | None | N |
| N/L | 0.8027 | likely_pathogenic | 0.8501 | pathogenic | -0.203 | Destabilizing | 0.995 | D | 0.764 | deleterious | None | None | None | None | N |
| N/M | 0.8605 | likely_pathogenic | 0.9 | pathogenic | 0.109 | Stabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| N/P | 0.99 | likely_pathogenic | 0.9929 | pathogenic | -0.49 | Destabilizing | 0.998 | D | 0.821 | deleterious | None | None | None | None | N |
| N/Q | 0.857 | likely_pathogenic | 0.8891 | pathogenic | -1.119 | Destabilizing | 0.998 | D | 0.717 | prob.delet. | None | None | None | None | N |
| N/R | 0.9046 | likely_pathogenic | 0.9249 | pathogenic | -0.357 | Destabilizing | 0.995 | D | 0.696 | prob.neutral | None | None | None | None | N |
| N/S | 0.1166 | likely_benign | 0.1477 | benign | -1.248 | Destabilizing | 0.362 | N | 0.364 | neutral | N | 0.471514361 | None | None | N |
| N/T | 0.5462 | ambiguous | 0.6725 | pathogenic | -0.885 | Destabilizing | 0.955 | D | 0.487 | neutral | N | 0.469764922 | None | None | N |
| N/V | 0.8631 | likely_pathogenic | 0.9006 | pathogenic | -0.49 | Destabilizing | 0.995 | D | 0.816 | deleterious | None | None | None | None | N |
| N/W | 0.9784 | likely_pathogenic | 0.9845 | pathogenic | -0.642 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| N/Y | 0.5968 | likely_pathogenic | 0.6557 | pathogenic | -0.335 | Destabilizing | 0.999 | D | 0.841 | deleterious | N | 0.481694069 | 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.