Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17063 | 51412;51413;51414 | chr2:178610339;178610338;178610337 | chr2:179475066;179475065;179475064 |
| N2AB | 15422 | 46489;46490;46491 | chr2:178610339;178610338;178610337 | chr2:179475066;179475065;179475064 |
| N2A | 14495 | 43708;43709;43710 | chr2:178610339;178610338;178610337 | chr2:179475066;179475065;179475064 |
| N2B | 7998 | 24217;24218;24219 | chr2:178610339;178610338;178610337 | chr2:179475066;179475065;179475064 |
| Novex-1 | 8123 | 24592;24593;24594 | chr2:178610339;178610338;178610337 | chr2:179475066;179475065;179475064 |
| Novex-2 | 8190 | 24793;24794;24795 | chr2:178610339;178610338;178610337 | chr2:179475066;179475065;179475064 |
| 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 | rs758563428  |
-0.568 | 0.991 | D | 0.734 | 0.506 | 0.485991781493 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/P | rs758563428 |
-0.568 | 0.991 | D | 0.734 | 0.506 | 0.485991781493 | gnomAD-4.0.0 | 1.36924E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31981E-05 | 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 | 0.1294 | likely_benign | 0.1482 | benign | -0.438 | Destabilizing | 0.76 | D | 0.419 | neutral | D | 0.533736764 | None | None | N |
| S/C | 0.1606 | likely_benign | 0.18 | benign | -0.8 | Destabilizing | 0.999 | D | 0.706 | prob.neutral | D | 0.525977492 | None | None | N |
| S/D | 0.8803 | likely_pathogenic | 0.8662 | pathogenic | -1.679 | Destabilizing | 0.953 | D | 0.543 | neutral | None | None | None | None | N |
| S/E | 0.8707 | likely_pathogenic | 0.8609 | pathogenic | -1.659 | Destabilizing | 0.953 | D | 0.553 | neutral | None | None | None | None | N |
| S/F | 0.3192 | likely_benign | 0.3489 | ambiguous | -0.934 | Destabilizing | 0.991 | D | 0.774 | deleterious | D | 0.535325896 | None | None | N |
| S/G | 0.1733 | likely_benign | 0.1918 | benign | -0.635 | Destabilizing | 0.953 | D | 0.447 | neutral | None | None | None | None | N |
| S/H | 0.5336 | ambiguous | 0.5355 | ambiguous | -1.21 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | N |
| S/I | 0.4815 | ambiguous | 0.4704 | ambiguous | -0.018 | Destabilizing | 0.986 | D | 0.761 | deleterious | None | None | None | None | N |
| S/K | 0.9487 | likely_pathogenic | 0.9443 | pathogenic | -0.622 | Destabilizing | 0.953 | D | 0.547 | neutral | None | None | None | None | N |
| S/L | 0.2169 | likely_benign | 0.231 | benign | -0.018 | Destabilizing | 0.91 | D | 0.659 | neutral | None | None | None | None | N |
| S/M | 0.286 | likely_benign | 0.3133 | benign | 0.251 | Stabilizing | 0.999 | D | 0.714 | prob.delet. | None | None | None | None | N |
| S/N | 0.3495 | ambiguous | 0.3592 | ambiguous | -0.976 | Destabilizing | 0.953 | D | 0.561 | neutral | None | None | None | None | N |
| S/P | 0.9947 | likely_pathogenic | 0.9926 | pathogenic | -0.128 | Destabilizing | 0.991 | D | 0.734 | prob.delet. | D | 0.732438225 | None | None | N |
| S/Q | 0.7195 | likely_pathogenic | 0.7323 | pathogenic | -1.243 | Destabilizing | 0.993 | D | 0.644 | neutral | None | None | None | None | N |
| S/R | 0.9253 | likely_pathogenic | 0.9152 | pathogenic | -0.448 | Destabilizing | 0.993 | D | 0.745 | deleterious | None | None | None | None | N |
| S/T | 0.1075 | likely_benign | 0.1002 | benign | -0.75 | Destabilizing | 0.079 | N | 0.259 | neutral | N | 0.487844986 | None | None | N |
| S/V | 0.4011 | ambiguous | 0.4041 | ambiguous | -0.128 | Destabilizing | 0.91 | D | 0.671 | neutral | None | None | None | None | N |
| S/W | 0.7056 | likely_pathogenic | 0.6773 | pathogenic | -1.059 | Destabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | N |
| S/Y | 0.3821 | ambiguous | 0.3917 | ambiguous | -0.646 | Destabilizing | 0.997 | D | 0.775 | deleterious | D | 0.558434942 | 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.