Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32816 | 98671;98672;98673 | chr2:178539619;178539618;178539617 | chr2:179404346;179404345;179404344 |
| N2AB | 31175 | 93748;93749;93750 | chr2:178539619;178539618;178539617 | chr2:179404346;179404345;179404344 |
| N2A | 30248 | 90967;90968;90969 | chr2:178539619;178539618;178539617 | chr2:179404346;179404345;179404344 |
| N2B | 23751 | 71476;71477;71478 | chr2:178539619;178539618;178539617 | chr2:179404346;179404345;179404344 |
| Novex-1 | 23876 | 71851;71852;71853 | chr2:178539619;178539618;178539617 | chr2:179404346;179404345;179404344 |
| Novex-2 | 23943 | 72052;72053;72054 | chr2:178539619;178539618;178539617 | chr2:179404346;179404345;179404344 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs773294476  |
-0.917 | 0.994 | N | 0.6 | 0.314 | 0.318252033908 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| S/N | rs773294476 |
-0.917 | 0.994 | N | 0.6 | 0.314 | 0.318252033908 | gnomAD-4.0.0 | 3.18246E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71631E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1281 | likely_benign | 0.1258 | benign | -0.817 | Destabilizing | 0.693 | D | 0.408 | neutral | None | None | None | None | N |
| S/C | 0.1394 | likely_benign | 0.1438 | benign | -0.568 | Destabilizing | 0.056 | N | 0.419 | neutral | N | 0.503104886 | None | None | N |
| S/D | 0.8148 | likely_pathogenic | 0.8452 | pathogenic | -0.892 | Destabilizing | 0.996 | D | 0.609 | neutral | None | None | None | None | N |
| S/E | 0.8434 | likely_pathogenic | 0.8716 | pathogenic | -0.754 | Destabilizing | 0.996 | D | 0.615 | neutral | None | None | None | None | N |
| S/F | 0.3462 | ambiguous | 0.355 | ambiguous | -0.707 | Destabilizing | 0.987 | D | 0.73 | prob.delet. | None | None | None | None | N |
| S/G | 0.1833 | likely_benign | 0.1836 | benign | -1.186 | Destabilizing | 0.944 | D | 0.454 | neutral | N | 0.493608232 | None | None | N |
| S/H | 0.5233 | ambiguous | 0.5643 | pathogenic | -1.538 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| S/I | 0.3205 | likely_benign | 0.3387 | benign | 0.099 | Stabilizing | 0.967 | D | 0.675 | neutral | N | 0.504332654 | None | None | N |
| S/K | 0.8584 | likely_pathogenic | 0.8902 | pathogenic | -0.362 | Destabilizing | 0.987 | D | 0.585 | neutral | None | None | None | None | N |
| S/L | 0.1886 | likely_benign | 0.1844 | benign | 0.099 | Stabilizing | 0.845 | D | 0.544 | neutral | None | None | None | None | N |
| S/M | 0.3303 | likely_benign | 0.3245 | benign | 0.113 | Stabilizing | 0.999 | D | 0.695 | prob.neutral | None | None | None | None | N |
| S/N | 0.3176 | likely_benign | 0.3251 | benign | -0.819 | Destabilizing | 0.994 | D | 0.6 | neutral | N | 0.481971984 | None | None | N |
| S/P | 0.9796 | likely_pathogenic | 0.9805 | pathogenic | -0.17 | Destabilizing | 0.996 | D | 0.671 | neutral | None | None | None | None | N |
| S/Q | 0.6993 | likely_pathogenic | 0.7273 | pathogenic | -0.703 | Destabilizing | 0.996 | D | 0.638 | neutral | None | None | None | None | N |
| S/R | 0.7542 | likely_pathogenic | 0.8102 | pathogenic | -0.586 | Destabilizing | 0.994 | D | 0.674 | neutral | N | 0.48671847 | None | None | N |
| S/T | 0.113 | likely_benign | 0.1151 | benign | -0.622 | Destabilizing | 0.892 | D | 0.473 | neutral | N | 0.498839822 | None | None | N |
| S/V | 0.3154 | likely_benign | 0.3233 | benign | -0.17 | Destabilizing | 0.975 | D | 0.597 | neutral | None | None | None | None | N |
| S/W | 0.5586 | ambiguous | 0.5933 | pathogenic | -0.843 | Destabilizing | 0.999 | D | 0.734 | prob.delet. | None | None | None | None | N |
| S/Y | 0.3666 | ambiguous | 0.3849 | ambiguous | -0.453 | Destabilizing | 0.996 | D | 0.729 | 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.