Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26693 | 80302;80303;80304 | chr2:178566055;178566054;178566053 | chr2:179430782;179430781;179430780 |
| N2AB | 25052 | 75379;75380;75381 | chr2:178566055;178566054;178566053 | chr2:179430782;179430781;179430780 |
| N2A | 24125 | 72598;72599;72600 | chr2:178566055;178566054;178566053 | chr2:179430782;179430781;179430780 |
| N2B | 17628 | 53107;53108;53109 | chr2:178566055;178566054;178566053 | chr2:179430782;179430781;179430780 |
| Novex-1 | 17753 | 53482;53483;53484 | chr2:178566055;178566054;178566053 | chr2:179430782;179430781;179430780 |
| Novex-2 | 17820 | 53683;53684;53685 | chr2:178566055;178566054;178566053 | chr2:179430782;179430781;179430780 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | None | None | 0.678 | N | 0.593 | 0.283 | 0.284539287134 | gnomAD-4.0.0 | 1.59171E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.773E-05 | None | 0 | 0 | 0 | 0 | 0 |
| K/R | rs544750835  |
0.039 | 0.009 | N | 0.291 | 0.103 | 0.17948927462 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| K/R | rs544750835 |
0.039 | 0.009 | N | 0.291 | 0.103 | 0.17948927462 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| K/R | rs544750835 |
0.039 | 0.009 | N | 0.291 | 0.103 | 0.17948927462 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| K/R | rs544750835 |
0.039 | 0.009 | N | 0.291 | 0.103 | 0.17948927462 | gnomAD-4.0.0 | 6.5678E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.4705E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.4602 | ambiguous | 0.4228 | ambiguous | -0.346 | Destabilizing | 0.823 | D | 0.61 | neutral | None | None | None | None | N |
| K/C | 0.6778 | likely_pathogenic | 0.7043 | pathogenic | -0.524 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| K/D | 0.7436 | likely_pathogenic | 0.7064 | pathogenic | 0.044 | Stabilizing | 0.97 | D | 0.605 | neutral | None | None | None | None | N |
| K/E | 0.31 | likely_benign | 0.2735 | benign | 0.148 | Stabilizing | 0.678 | D | 0.593 | neutral | N | 0.493487144 | None | None | N |
| K/F | 0.8544 | likely_pathogenic | 0.8425 | pathogenic | -0.129 | Destabilizing | 0.963 | D | 0.711 | prob.delet. | None | None | None | None | N |
| K/G | 0.519 | ambiguous | 0.4975 | ambiguous | -0.665 | Destabilizing | 0.823 | D | 0.583 | neutral | None | None | None | None | N |
| K/H | 0.3214 | likely_benign | 0.3256 | benign | -0.791 | Destabilizing | 0.997 | D | 0.651 | neutral | None | None | None | None | N |
| K/I | 0.4956 | ambiguous | 0.4658 | ambiguous | 0.461 | Stabilizing | 0.595 | D | 0.715 | prob.delet. | N | 0.468570854 | None | None | N |
| K/L | 0.4641 | ambiguous | 0.4496 | ambiguous | 0.461 | Stabilizing | 0.215 | N | 0.581 | neutral | None | None | None | None | N |
| K/M | 0.3341 | likely_benign | 0.3011 | benign | 0.032 | Stabilizing | 0.989 | D | 0.642 | neutral | None | None | None | None | N |
| K/N | 0.5376 | ambiguous | 0.5079 | ambiguous | -0.302 | Destabilizing | 0.961 | D | 0.629 | neutral | N | 0.475345257 | None | None | N |
| K/P | 0.9205 | likely_pathogenic | 0.9153 | pathogenic | 0.222 | Stabilizing | 0.985 | D | 0.676 | prob.neutral | None | None | None | None | N |
| K/Q | 0.1639 | likely_benign | 0.1542 | benign | -0.295 | Destabilizing | 0.749 | D | 0.639 | neutral | N | 0.519116307 | None | None | N |
| K/R | 0.0777 | likely_benign | 0.0777 | benign | -0.306 | Destabilizing | 0.009 | N | 0.291 | neutral | N | 0.503608137 | None | None | N |
| K/S | 0.4564 | ambiguous | 0.433 | ambiguous | -0.86 | Destabilizing | 0.224 | N | 0.312 | neutral | None | None | None | None | N |
| K/T | 0.1865 | likely_benign | 0.1621 | benign | -0.558 | Destabilizing | 0.513 | D | 0.623 | neutral | N | 0.426376717 | None | None | N |
| K/V | 0.427 | ambiguous | 0.397 | ambiguous | 0.222 | Stabilizing | 0.558 | D | 0.613 | neutral | None | None | None | None | N |
| K/W | 0.7911 | likely_pathogenic | 0.7896 | pathogenic | -0.098 | Destabilizing | 0.999 | D | 0.739 | prob.delet. | None | None | None | None | N |
| K/Y | 0.7239 | likely_pathogenic | 0.7191 | pathogenic | 0.206 | Stabilizing | 0.904 | D | 0.709 | prob.delet. | 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.