Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31573 | 94942;94943;94944 | chr2:178546711;178546710;178546709 | chr2:179411438;179411437;179411436 |
| N2AB | 29932 | 90019;90020;90021 | chr2:178546711;178546710;178546709 | chr2:179411438;179411437;179411436 |
| N2A | 29005 | 87238;87239;87240 | chr2:178546711;178546710;178546709 | chr2:179411438;179411437;179411436 |
| N2B | 22508 | 67747;67748;67749 | chr2:178546711;178546710;178546709 | chr2:179411438;179411437;179411436 |
| Novex-1 | 22633 | 68122;68123;68124 | chr2:178546711;178546710;178546709 | chr2:179411438;179411437;179411436 |
| Novex-2 | 22700 | 68323;68324;68325 | chr2:178546711;178546710;178546709 | chr2:179411438;179411437;179411436 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs1175642523  |
-0.262 | 0.852 | N | 0.344 | 0.199 | 0.225902525712 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| A/T | rs1175642523 |
-0.262 | 0.852 | N | 0.344 | 0.199 | 0.225902525712 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/T | rs1175642523 |
-0.262 | 0.852 | N | 0.344 | 0.199 | 0.225902525712 | gnomAD-4.0.0 | 3.09847E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23812E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7288 | likely_pathogenic | 0.7121 | pathogenic | -0.761 | Destabilizing | 0.999 | D | 0.423 | neutral | None | None | None | None | N |
| A/D | 0.7971 | likely_pathogenic | 0.7385 | pathogenic | -0.266 | Destabilizing | 0.852 | D | 0.414 | neutral | N | 0.346371564 | None | None | N |
| A/E | 0.7726 | likely_pathogenic | 0.7374 | pathogenic | -0.416 | Destabilizing | 0.939 | D | 0.408 | neutral | None | None | None | None | N |
| A/F | 0.7863 | likely_pathogenic | 0.741 | pathogenic | -0.799 | Destabilizing | 0.997 | D | 0.463 | neutral | None | None | None | None | N |
| A/G | 0.1875 | likely_benign | 0.1724 | benign | -0.189 | Destabilizing | 0.015 | N | 0.12 | neutral | N | 0.273468529 | None | None | N |
| A/H | 0.8434 | likely_pathogenic | 0.8168 | pathogenic | -0.222 | Destabilizing | 0.998 | D | 0.465 | neutral | None | None | None | None | N |
| A/I | 0.8404 | likely_pathogenic | 0.7729 | pathogenic | -0.27 | Destabilizing | 0.991 | D | 0.461 | neutral | None | None | None | None | N |
| A/K | 0.9464 | likely_pathogenic | 0.926 | pathogenic | -0.479 | Destabilizing | 0.939 | D | 0.416 | neutral | None | None | None | None | N |
| A/L | 0.5402 | ambiguous | 0.4787 | ambiguous | -0.27 | Destabilizing | 0.969 | D | 0.416 | neutral | None | None | None | None | N |
| A/M | 0.6013 | likely_pathogenic | 0.549 | ambiguous | -0.409 | Destabilizing | 0.999 | D | 0.443 | neutral | None | None | None | None | N |
| A/N | 0.4961 | ambiguous | 0.4607 | ambiguous | -0.182 | Destabilizing | 0.17 | N | 0.339 | neutral | None | None | None | None | N |
| A/P | 0.9154 | likely_pathogenic | 0.8337 | pathogenic | -0.202 | Destabilizing | 0.988 | D | 0.472 | neutral | N | 0.455080684 | None | None | N |
| A/Q | 0.7075 | likely_pathogenic | 0.6843 | pathogenic | -0.43 | Destabilizing | 0.991 | D | 0.457 | neutral | None | None | None | None | N |
| A/R | 0.9039 | likely_pathogenic | 0.8764 | pathogenic | -0.078 | Destabilizing | 0.991 | D | 0.46 | neutral | None | None | None | None | N |
| A/S | 0.1201 | likely_benign | 0.1125 | benign | -0.397 | Destabilizing | 0.159 | N | 0.141 | neutral | N | 0.410039041 | None | None | N |
| A/T | 0.2828 | likely_benign | 0.2416 | benign | -0.464 | Destabilizing | 0.852 | D | 0.344 | neutral | N | 0.455254043 | None | None | N |
| A/V | 0.5515 | ambiguous | 0.4673 | ambiguous | -0.202 | Destabilizing | 0.959 | D | 0.405 | neutral | N | 0.508029735 | None | None | N |
| A/W | 0.9723 | likely_pathogenic | 0.9626 | pathogenic | -0.934 | Destabilizing | 0.999 | D | 0.607 | neutral | None | None | None | None | N |
| A/Y | 0.8628 | likely_pathogenic | 0.8326 | pathogenic | -0.583 | Destabilizing | 0.997 | D | 0.465 | 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.