Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15249 | 45970;45971;45972 | chr2:178620865;178620864;178620863 | chr2:179485592;179485591;179485590 |
| N2AB | 13608 | 41047;41048;41049 | chr2:178620865;178620864;178620863 | chr2:179485592;179485591;179485590 |
| N2A | 12681 | 38266;38267;38268 | chr2:178620865;178620864;178620863 | chr2:179485592;179485591;179485590 |
| N2B | 6184 | 18775;18776;18777 | chr2:178620865;178620864;178620863 | chr2:179485592;179485591;179485590 |
| Novex-1 | 6309 | 19150;19151;19152 | chr2:178620865;178620864;178620863 | chr2:179485592;179485591;179485590 |
| Novex-2 | 6376 | 19351;19352;19353 | chr2:178620865;178620864;178620863 | chr2:179485592;179485591;179485590 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | rs1467540790  |
None | 1.0 | N | 0.548 | 0.424 | 0.42324137094 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/H | rs1467540790 |
None | 1.0 | N | 0.548 | 0.424 | 0.42324137094 | gnomAD-4.0.0 | 6.58623E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47262E-05 | 0 | 0 |
| D/N | None | None | 0.989 | N | 0.424 | 0.32 | 0.413113201963 | gnomAD-4.0.0 | 1.59361E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43345E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3044 | likely_benign | 0.3699 | ambiguous | -0.327 | Destabilizing | 0.978 | D | 0.481 | neutral | N | 0.499812069 | None | None | N |
| D/C | 0.8652 | likely_pathogenic | 0.8867 | pathogenic | -0.087 | Destabilizing | 1.0 | D | 0.614 | neutral | None | None | None | None | N |
| D/E | 0.2303 | likely_benign | 0.3129 | benign | -0.266 | Destabilizing | 0.198 | N | 0.213 | neutral | N | 0.425750098 | None | None | N |
| D/F | 0.8414 | likely_pathogenic | 0.8714 | pathogenic | -0.065 | Destabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | N |
| D/G | 0.3284 | likely_benign | 0.3766 | ambiguous | -0.539 | Destabilizing | 0.989 | D | 0.491 | neutral | D | 0.556654638 | None | None | N |
| D/H | 0.5186 | ambiguous | 0.5783 | pathogenic | 0.196 | Stabilizing | 1.0 | D | 0.548 | neutral | N | 0.51082682 | None | None | N |
| D/I | 0.6666 | likely_pathogenic | 0.7405 | pathogenic | 0.19 | Stabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | N |
| D/K | 0.6745 | likely_pathogenic | 0.7352 | pathogenic | 0.416 | Stabilizing | 0.983 | D | 0.493 | neutral | None | None | None | None | N |
| D/L | 0.6451 | likely_pathogenic | 0.6977 | pathogenic | 0.19 | Stabilizing | 0.998 | D | 0.64 | neutral | None | None | None | None | N |
| D/M | 0.8927 | likely_pathogenic | 0.9214 | pathogenic | 0.235 | Stabilizing | 1.0 | D | 0.607 | neutral | None | None | None | None | N |
| D/N | 0.1718 | likely_benign | 0.2169 | benign | -0.142 | Destabilizing | 0.989 | D | 0.424 | neutral | N | 0.494176172 | None | None | N |
| D/P | 0.5686 | likely_pathogenic | 0.6253 | pathogenic | 0.039 | Stabilizing | 0.999 | D | 0.561 | neutral | None | None | None | None | N |
| D/Q | 0.5753 | likely_pathogenic | 0.644 | pathogenic | -0.064 | Destabilizing | 0.995 | D | 0.465 | neutral | None | None | None | None | N |
| D/R | 0.6737 | likely_pathogenic | 0.7085 | pathogenic | 0.622 | Stabilizing | 0.995 | D | 0.58 | neutral | None | None | None | None | N |
| D/S | 0.2104 | likely_benign | 0.2619 | benign | -0.194 | Destabilizing | 0.983 | D | 0.385 | neutral | None | None | None | None | N |
| D/T | 0.4697 | ambiguous | 0.5489 | ambiguous | -0.011 | Destabilizing | 0.998 | D | 0.507 | neutral | None | None | None | None | N |
| D/V | 0.4607 | ambiguous | 0.534 | ambiguous | 0.039 | Stabilizing | 0.997 | D | 0.634 | neutral | N | 0.510673167 | None | None | N |
| D/W | 0.9664 | likely_pathogenic | 0.969 | pathogenic | 0.134 | Stabilizing | 1.0 | D | 0.607 | neutral | None | None | None | None | N |
| D/Y | 0.4521 | ambiguous | 0.4838 | ambiguous | 0.192 | Stabilizing | 1.0 | D | 0.619 | neutral | D | 0.55875195 | 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.