Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31851 | 95776;95777;95778 | chr2:178545559;178545558;178545557 | chr2:179410286;179410285;179410284 |
| N2AB | 30210 | 90853;90854;90855 | chr2:178545559;178545558;178545557 | chr2:179410286;179410285;179410284 |
| N2A | 29283 | 88072;88073;88074 | chr2:178545559;178545558;178545557 | chr2:179410286;179410285;179410284 |
| N2B | 22786 | 68581;68582;68583 | chr2:178545559;178545558;178545557 | chr2:179410286;179410285;179410284 |
| Novex-1 | 22911 | 68956;68957;68958 | chr2:178545559;178545558;178545557 | chr2:179410286;179410285;179410284 |
| Novex-2 | 22978 | 69157;69158;69159 | chr2:178545559;178545558;178545557 | chr2:179410286;179410285;179410284 |
| 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 | rs746468000  |
-0.357 | 0.999 | N | 0.465 | 0.26 | 0.207176502487 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/N | rs746468000 |
-0.357 | 0.999 | N | 0.465 | 0.26 | 0.207176502487 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07555E-04 | 0 |
| S/N | rs746468000 |
-0.357 | 0.999 | N | 0.465 | 0.26 | 0.207176502487 | gnomAD-4.0.0 | 1.23945E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.09801E-05 | 1.60128E-05 |
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 | 0.181 | likely_benign | 0.1642 | benign | -0.32 | Destabilizing | 0.998 | D | 0.374 | neutral | None | None | None | None | N |
| S/C | 0.1968 | likely_benign | 0.2241 | benign | -0.349 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | N | 0.499934427 | None | None | N |
| S/D | 0.8713 | likely_pathogenic | 0.8725 | pathogenic | 0.343 | Stabilizing | 0.999 | D | 0.493 | neutral | None | None | None | None | N |
| S/E | 0.9339 | likely_pathogenic | 0.935 | pathogenic | 0.251 | Stabilizing | 0.999 | D | 0.471 | neutral | None | None | None | None | N |
| S/F | 0.6881 | likely_pathogenic | 0.6215 | pathogenic | -0.849 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| S/G | 0.0936 | likely_benign | 0.0982 | benign | -0.433 | Destabilizing | 0.999 | D | 0.362 | neutral | N | 0.439711374 | None | None | N |
| S/H | 0.7663 | likely_pathogenic | 0.754 | pathogenic | -0.853 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| S/I | 0.6354 | likely_pathogenic | 0.6207 | pathogenic | -0.156 | Destabilizing | 1.0 | D | 0.649 | neutral | N | 0.503466372 | None | None | N |
| S/K | 0.9723 | likely_pathogenic | 0.9724 | pathogenic | -0.446 | Destabilizing | 0.999 | D | 0.482 | neutral | None | None | None | None | N |
| S/L | 0.348 | ambiguous | 0.2908 | benign | -0.156 | Destabilizing | 1.0 | D | 0.565 | neutral | None | None | None | None | N |
| S/M | 0.4587 | ambiguous | 0.4221 | ambiguous | -0.045 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| S/N | 0.3591 | ambiguous | 0.3466 | ambiguous | -0.162 | Destabilizing | 0.999 | D | 0.465 | neutral | N | 0.480700855 | None | None | N |
| S/P | 0.9457 | likely_pathogenic | 0.9384 | pathogenic | -0.182 | Destabilizing | 1.0 | D | 0.614 | neutral | None | None | None | None | N |
| S/Q | 0.8738 | likely_pathogenic | 0.8666 | pathogenic | -0.396 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | N |
| S/R | 0.9641 | likely_pathogenic | 0.9618 | pathogenic | -0.243 | Destabilizing | 1.0 | D | 0.611 | neutral | N | 0.475447389 | None | None | N |
| S/T | 0.2005 | likely_benign | 0.189 | benign | -0.303 | Destabilizing | 0.999 | D | 0.347 | neutral | N | 0.504589572 | None | None | N |
| S/V | 0.5793 | likely_pathogenic | 0.5557 | ambiguous | -0.182 | Destabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | N |
| S/W | 0.8258 | likely_pathogenic | 0.7887 | pathogenic | -0.848 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| S/Y | 0.5875 | likely_pathogenic | 0.5332 | ambiguous | -0.571 | Destabilizing | 1.0 | D | 0.726 | 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.