Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19128 | 57607;57608;57609 | chr2:178597700;178597699;178597698 | chr2:179462427;179462426;179462425 |
| N2AB | 17487 | 52684;52685;52686 | chr2:178597700;178597699;178597698 | chr2:179462427;179462426;179462425 |
| N2A | 16560 | 49903;49904;49905 | chr2:178597700;178597699;178597698 | chr2:179462427;179462426;179462425 |
| N2B | 10063 | 30412;30413;30414 | chr2:178597700;178597699;178597698 | chr2:179462427;179462426;179462425 |
| Novex-1 | 10188 | 30787;30788;30789 | chr2:178597700;178597699;178597698 | chr2:179462427;179462426;179462425 |
| Novex-2 | 10255 | 30988;30989;30990 | chr2:178597700;178597699;178597698 | chr2:179462427;179462426;179462425 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/L | rs138367112  |
None | 0.003 | N | 0.312 | 0.127 | 0.273938319068 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/L | rs138367112 |
None | 0.003 | N | 0.312 | 0.127 | 0.273938319068 | gnomAD-4.0.0 | 1.85959E-06 | None | None | None | None | N | None | 1.33504E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69555E-06 | 0 | 0 |
| M/V | rs138367112 |
-1.018 | 0.006 | N | 0.315 | 0.1 | None | gnomAD-2.1.1 | 3.58E-05 | None | None | None | None | N | None | 3.30715E-04 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.40489E-04 |
| M/V | rs138367112 |
-1.018 | 0.006 | N | 0.315 | 0.1 | None | gnomAD-3.1.2 | 1.05201E-04 | None | None | None | None | N | None | 3.3774E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.79386E-04 |
| M/V | rs138367112 |
-1.018 | 0.006 | N | 0.315 | 0.1 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| M/V | rs138367112 |
-1.018 | 0.006 | N | 0.315 | 0.1 | None | gnomAD-4.0.0 | 2.35531E-05 | None | None | None | None | N | None | 3.59875E-04 | 5.00334E-05 | None | 0 | 0 | None | 0 | 0 | 8.47781E-07 | 2.19606E-05 | 8.00538E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5286 | ambiguous | 0.5913 | pathogenic | -2.01 | Highly Destabilizing | 0.004 | N | 0.323 | neutral | None | None | None | None | N |
| M/C | 0.4808 | ambiguous | 0.4051 | ambiguous | -1.995 | Destabilizing | 0.497 | N | 0.561 | neutral | None | None | None | None | N |
| M/D | 0.9447 | likely_pathogenic | 0.9511 | pathogenic | -1.521 | Destabilizing | 0.018 | N | 0.514 | neutral | None | None | None | None | N |
| M/E | 0.6526 | likely_pathogenic | 0.692 | pathogenic | -1.419 | Destabilizing | 0.004 | N | 0.385 | neutral | None | None | None | None | N |
| M/F | 0.2844 | likely_benign | 0.3174 | benign | -0.97 | Destabilizing | 0.22 | N | 0.479 | neutral | None | None | None | None | N |
| M/G | 0.7702 | likely_pathogenic | 0.8299 | pathogenic | -2.389 | Highly Destabilizing | 0.018 | N | 0.423 | neutral | None | None | None | None | N |
| M/H | 0.4178 | ambiguous | 0.3763 | ambiguous | -1.742 | Destabilizing | 0.245 | N | 0.591 | neutral | None | None | None | None | N |
| M/I | 0.3765 | ambiguous | 0.4331 | ambiguous | -0.981 | Destabilizing | 0.028 | N | 0.35 | neutral | N | 0.407953167 | None | None | N |
| M/K | 0.0927 | likely_benign | 0.115 | benign | -0.947 | Destabilizing | None | N | 0.193 | neutral | N | 0.259450721 | None | None | N |
| M/L | 0.1684 | likely_benign | 0.1887 | benign | -0.981 | Destabilizing | 0.003 | N | 0.312 | neutral | N | 0.363546242 | None | None | N |
| M/N | 0.704 | likely_pathogenic | 0.6928 | pathogenic | -1.022 | Destabilizing | 0.018 | N | 0.429 | neutral | None | None | None | None | N |
| M/P | 0.975 | likely_pathogenic | 0.9891 | pathogenic | -1.301 | Destabilizing | 0.085 | N | 0.521 | neutral | None | None | None | None | N |
| M/Q | 0.1908 | likely_benign | 0.1823 | benign | -1.0 | Destabilizing | 0.009 | N | 0.337 | neutral | None | None | None | None | N |
| M/R | 0.0929 | likely_benign | 0.1148 | benign | -0.727 | Destabilizing | None | N | 0.18 | neutral | N | 0.278850132 | None | None | N |
| M/S | 0.6474 | likely_pathogenic | 0.6603 | pathogenic | -1.632 | Destabilizing | 0.004 | N | 0.363 | neutral | None | None | None | None | N |
| M/T | 0.4156 | ambiguous | 0.4893 | ambiguous | -1.41 | Destabilizing | 0.014 | N | 0.377 | neutral | N | 0.438102716 | None | None | N |
| M/V | 0.117 | likely_benign | 0.1358 | benign | -1.301 | Destabilizing | 0.006 | N | 0.315 | neutral | N | 0.407953167 | None | None | N |
| M/W | 0.5121 | ambiguous | 0.5633 | ambiguous | -1.077 | Destabilizing | 0.788 | D | 0.539 | neutral | None | None | None | None | N |
| M/Y | 0.4602 | ambiguous | 0.4517 | ambiguous | -1.031 | Destabilizing | 0.22 | N | 0.579 | 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.