Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32985 | 99178;99179;99180 | chr2:178538982;178538981;178538980 | chr2:179403709;179403708;179403707 |
| N2AB | 31344 | 94255;94256;94257 | chr2:178538982;178538981;178538980 | chr2:179403709;179403708;179403707 |
| N2A | 30417 | 91474;91475;91476 | chr2:178538982;178538981;178538980 | chr2:179403709;179403708;179403707 |
| N2B | 23920 | 71983;71984;71985 | chr2:178538982;178538981;178538980 | chr2:179403709;179403708;179403707 |
| Novex-1 | 24045 | 72358;72359;72360 | chr2:178538982;178538981;178538980 | chr2:179403709;179403708;179403707 |
| Novex-2 | 24112 | 72559;72560;72561 | chr2:178538982;178538981;178538980 | chr2:179403709;179403708;179403707 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/H | rs1387380794  |
-0.24 | 1.0 | N | 0.8 | 0.308 | 0.547254970357 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/H | rs1387380794 |
-0.24 | 1.0 | N | 0.8 | 0.308 | 0.547254970357 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/H | rs1387380794 |
-0.24 | 1.0 | N | 0.8 | 0.308 | 0.547254970357 | gnomAD-4.0.0 | 1.30277E-05 | None | None | None | None | N | None | 8.01368E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.27301E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0964 | likely_benign | 0.0962 | benign | -1.27 | Destabilizing | 0.991 | D | 0.711 | prob.delet. | N | 0.46924206 | None | None | N |
| P/C | 0.6597 | likely_pathogenic | 0.6037 | pathogenic | -0.881 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| P/D | 0.5916 | likely_pathogenic | 0.5473 | ambiguous | -0.812 | Destabilizing | 0.998 | D | 0.683 | prob.neutral | None | None | None | None | N |
| P/E | 0.3212 | likely_benign | 0.3041 | benign | -0.866 | Destabilizing | 0.987 | D | 0.749 | deleterious | None | None | None | None | N |
| P/F | 0.5912 | likely_pathogenic | 0.5402 | ambiguous | -1.155 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| P/G | 0.448 | ambiguous | 0.4334 | ambiguous | -1.518 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | None | None | None | None | N |
| P/H | 0.3155 | likely_benign | 0.2811 | benign | -0.994 | Destabilizing | 1.0 | D | 0.8 | deleterious | N | 0.511552829 | None | None | N |
| P/I | 0.3342 | likely_benign | 0.3111 | benign | -0.715 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| P/K | 0.3949 | ambiguous | 0.3597 | ambiguous | -0.885 | Destabilizing | 0.996 | D | 0.74 | deleterious | None | None | None | None | N |
| P/L | 0.1325 | likely_benign | 0.1242 | benign | -0.715 | Destabilizing | 0.999 | D | 0.734 | deleterious | N | 0.479112337 | None | None | N |
| P/M | 0.3376 | likely_benign | 0.3246 | benign | -0.521 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| P/N | 0.4831 | ambiguous | 0.4534 | ambiguous | -0.598 | Destabilizing | 0.999 | D | 0.766 | deleterious | None | None | None | None | N |
| P/Q | 0.2007 | likely_benign | 0.1881 | benign | -0.85 | Destabilizing | 0.969 | D | 0.573 | neutral | None | None | None | None | N |
| P/R | 0.2937 | likely_benign | 0.2593 | benign | -0.351 | Destabilizing | 0.997 | D | 0.781 | deleterious | N | 0.478266975 | None | None | N |
| P/S | 0.1782 | likely_benign | 0.1665 | benign | -1.13 | Destabilizing | 0.997 | D | 0.731 | deleterious | N | 0.476418749 | None | None | N |
| P/T | 0.1378 | likely_benign | 0.1288 | benign | -1.08 | Destabilizing | 0.999 | D | 0.694 | prob.delet. | N | 0.473879876 | None | None | N |
| P/V | 0.2191 | likely_benign | 0.2138 | benign | -0.865 | Destabilizing | 0.999 | D | 0.747 | deleterious | None | None | None | None | N |
| P/W | 0.8029 | likely_pathogenic | 0.7575 | pathogenic | -1.228 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| P/Y | 0.5944 | likely_pathogenic | 0.5375 | ambiguous | -0.949 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | 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.