Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14967 | 45124;45125;45126 | chr2:178622684;178622683;178622682 | chr2:179487411;179487410;179487409 |
| N2AB | 13326 | 40201;40202;40203 | chr2:178622684;178622683;178622682 | chr2:179487411;179487410;179487409 |
| N2A | 12399 | 37420;37421;37422 | chr2:178622684;178622683;178622682 | chr2:179487411;179487410;179487409 |
| N2B | 5902 | 17929;17930;17931 | chr2:178622684;178622683;178622682 | chr2:179487411;179487410;179487409 |
| Novex-1 | 6027 | 18304;18305;18306 | chr2:178622684;178622683;178622682 | chr2:179487411;179487410;179487409 |
| Novex-2 | 6094 | 18505;18506;18507 | chr2:178622684;178622683;178622682 | chr2:179487411;179487410;179487409 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | None | None | 0.561 | D | 0.487 | 0.279 | 0.460526725402 | gnomAD-4.0.0 | 1.37593E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80521E-06 | 0 | 0 |
| R/Q | rs752671402  |
0.014 | 0.832 | D | 0.595 | 0.149 | 0.270889551736 | gnomAD-2.1.1 | 5.18E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.94E-05 | None | 3.65913E-04 | 2.42E-05 | 0 |
| R/Q | rs752671402 |
0.014 | 0.832 | D | 0.595 | 0.149 | 0.270889551736 | gnomAD-3.1.2 | 4.62E-05 | None | None | None | None | N | None | 4.85E-05 | 0 | 0 | 0 | 0 | None | 1.89681E-04 | 0 | 4.42E-05 | 0 | 0 |
| R/Q | rs752671402 |
0.014 | 0.832 | D | 0.595 | 0.149 | 0.270889551736 | gnomAD-4.0.0 | 3.17741E-05 | None | None | None | None | N | None | 2.68449E-05 | 1.6889E-05 | None | 0 | 0 | None | 3.30272E-04 | 0 | 1.78612E-05 | 2.23639E-05 | 6.44538E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5371 | ambiguous | 0.4826 | ambiguous | 0.035 | Stabilizing | 0.25 | N | 0.517 | neutral | None | None | None | None | N |
| R/C | 0.3612 | ambiguous | 0.3506 | ambiguous | -0.088 | Destabilizing | 0.982 | D | 0.624 | neutral | None | None | None | None | N |
| R/D | 0.8188 | likely_pathogenic | 0.7774 | pathogenic | 0.004 | Stabilizing | 0.7 | D | 0.544 | neutral | None | None | None | None | N |
| R/E | 0.4623 | ambiguous | 0.4048 | ambiguous | 0.074 | Stabilizing | 0.25 | N | 0.538 | neutral | None | None | None | None | N |
| R/F | 0.7623 | likely_pathogenic | 0.708 | pathogenic | -0.17 | Destabilizing | 0.935 | D | 0.607 | neutral | None | None | None | None | N |
| R/G | 0.4181 | ambiguous | 0.3508 | ambiguous | -0.169 | Destabilizing | 0.561 | D | 0.487 | neutral | N | 0.43741367 | None | None | N |
| R/H | 0.2011 | likely_benign | 0.1892 | benign | -0.69 | Destabilizing | 0.826 | D | 0.558 | neutral | None | None | None | None | N |
| R/I | 0.4536 | ambiguous | 0.386 | ambiguous | 0.537 | Stabilizing | 0.826 | D | 0.623 | neutral | None | None | None | None | N |
| R/K | 0.1634 | likely_benign | 0.1521 | benign | 0.013 | Stabilizing | 0.002 | N | 0.2 | neutral | None | None | None | None | N |
| R/L | 0.3777 | ambiguous | 0.3376 | benign | 0.537 | Stabilizing | 0.561 | D | 0.487 | neutral | D | 0.625974946 | None | None | N |
| R/M | 0.4683 | ambiguous | 0.4079 | ambiguous | 0.085 | Stabilizing | 0.982 | D | 0.499 | neutral | None | None | None | None | N |
| R/N | 0.7902 | likely_pathogenic | 0.7511 | pathogenic | 0.24 | Stabilizing | 0.7 | D | 0.572 | neutral | None | None | None | None | N |
| R/P | 0.7436 | likely_pathogenic | 0.7311 | pathogenic | 0.39 | Stabilizing | 0.901 | D | 0.56 | neutral | D | 0.571733012 | None | None | N |
| R/Q | 0.1431 | likely_benign | 0.1332 | benign | 0.15 | Stabilizing | 0.832 | D | 0.595 | neutral | D | 0.536114762 | None | None | N |
| R/S | 0.657 | likely_pathogenic | 0.593 | pathogenic | -0.12 | Destabilizing | 0.25 | N | 0.537 | neutral | None | None | None | None | N |
| R/T | 0.4037 | ambiguous | 0.3384 | benign | 0.089 | Stabilizing | 0.7 | D | 0.503 | neutral | None | None | None | None | N |
| R/V | 0.5003 | ambiguous | 0.4489 | ambiguous | 0.39 | Stabilizing | 0.7 | D | 0.605 | neutral | None | None | None | None | N |
| R/W | 0.3125 | likely_benign | 0.2638 | benign | -0.225 | Destabilizing | 0.982 | D | 0.627 | neutral | None | None | None | None | N |
| R/Y | 0.6508 | likely_pathogenic | 0.6086 | pathogenic | 0.193 | Stabilizing | 0.935 | D | 0.565 | neutral | 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.