Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13702 | 41329;41330;41331 | chr2:178636623;178636622;178636621 | chr2:179501350;179501349;179501348 |
| N2AB | 12061 | 36406;36407;36408 | chr2:178636623;178636622;178636621 | chr2:179501350;179501349;179501348 |
| N2A | 11134 | 33625;33626;33627 | chr2:178636623;178636622;178636621 | chr2:179501350;179501349;179501348 |
| N2B | 4637 | 14134;14135;14136 | chr2:178636623;178636622;178636621 | chr2:179501350;179501349;179501348 |
| Novex-1 | 4762 | 14509;14510;14511 | chr2:178636623;178636622;178636621 | chr2:179501350;179501349;179501348 |
| Novex-2 | 4829 | 14710;14711;14712 | chr2:178636623;178636622;178636621 | chr2:179501350;179501349;179501348 |
| 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/P | rs72650078  |
-0.375 | 0.999 | D | 0.647 | 0.463 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/P | rs72650078 |
-0.375 | 0.999 | D | 0.647 | 0.463 | None |
Begay (2015)
Zuo (2021)
| None |
DCM 
|
het | None | None | N | WGS prioritisation; filtering with ANNOVAR; co-segregates within 2-generation family (n = 2, 2 affected (total 3)); moderate destabilisation of domain (SM-AFM) | None | None | None | None | None | None | None | None | None | None | None |
| S/P | rs72650078 |
-0.375 | 0.999 | D | 0.647 | 0.463 | None | gnomAD-4.0.0 | 6.40861E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.19705E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1066 | likely_benign | 0.1301 | benign | -0.669 | Destabilizing | 0.973 | D | 0.367 | neutral | N | 0.4562549 | None | None | N |
| S/C | 0.2945 | likely_benign | 0.3807 | ambiguous | -0.463 | Destabilizing | 1.0 | D | 0.651 | neutral | D | 0.556118574 | None | None | N |
| S/D | 0.5636 | ambiguous | 0.7438 | pathogenic | 0.058 | Stabilizing | 0.996 | D | 0.527 | neutral | None | None | None | None | N |
| S/E | 0.6372 | likely_pathogenic | 0.7789 | pathogenic | 0.001 | Stabilizing | 0.996 | D | 0.52 | neutral | None | None | None | None | N |
| S/F | 0.4453 | ambiguous | 0.6442 | pathogenic | -1.162 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | D | 0.532893133 | None | None | N |
| S/G | 0.1329 | likely_benign | 0.1809 | benign | -0.828 | Destabilizing | 0.996 | D | 0.423 | neutral | None | None | None | None | N |
| S/H | 0.5436 | ambiguous | 0.6816 | pathogenic | -1.4 | Destabilizing | 1.0 | D | 0.646 | neutral | None | None | None | None | N |
| S/I | 0.4173 | ambiguous | 0.5855 | pathogenic | -0.367 | Destabilizing | 0.998 | D | 0.704 | prob.neutral | None | None | None | None | N |
| S/K | 0.7738 | likely_pathogenic | 0.8917 | pathogenic | -0.526 | Destabilizing | 0.996 | D | 0.522 | neutral | None | None | None | None | N |
| S/L | 0.2262 | likely_benign | 0.3271 | benign | -0.367 | Destabilizing | 0.992 | D | 0.53 | neutral | None | None | None | None | N |
| S/M | 0.3967 | ambiguous | 0.5063 | ambiguous | 0.001 | Stabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | N |
| S/N | 0.2028 | likely_benign | 0.3171 | benign | -0.37 | Destabilizing | 0.996 | D | 0.521 | neutral | None | None | None | None | N |
| S/P | 0.5141 | ambiguous | 0.7484 | pathogenic | -0.437 | Destabilizing | 0.999 | D | 0.647 | neutral | D | 0.554436077 | None | None | N |
| S/Q | 0.5907 | likely_pathogenic | 0.7093 | pathogenic | -0.619 | Destabilizing | 1.0 | D | 0.646 | neutral | None | None | None | None | N |
| S/R | 0.7313 | likely_pathogenic | 0.8575 | pathogenic | -0.39 | Destabilizing | 0.999 | D | 0.656 | neutral | None | None | None | None | N |
| S/T | 0.1134 | likely_benign | 0.1567 | benign | -0.474 | Destabilizing | 0.543 | D | 0.315 | neutral | N | 0.452604178 | None | None | N |
| S/V | 0.3464 | ambiguous | 0.5096 | ambiguous | -0.437 | Destabilizing | 0.998 | D | 0.602 | neutral | None | None | None | None | N |
| S/W | 0.6971 | likely_pathogenic | 0.8341 | pathogenic | -1.099 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| S/Y | 0.3975 | ambiguous | 0.5577 | ambiguous | -0.835 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | N | 0.474803781 | 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.