Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24578 | 73957;73958;73959 | chr2:178572400;178572399;178572398 | chr2:179437127;179437126;179437125 |
| N2AB | 22937 | 69034;69035;69036 | chr2:178572400;178572399;178572398 | chr2:179437127;179437126;179437125 |
| N2A | 22010 | 66253;66254;66255 | chr2:178572400;178572399;178572398 | chr2:179437127;179437126;179437125 |
| N2B | 15513 | 46762;46763;46764 | chr2:178572400;178572399;178572398 | chr2:179437127;179437126;179437125 |
| Novex-1 | 15638 | 47137;47138;47139 | chr2:178572400;178572399;178572398 | chr2:179437127;179437126;179437125 |
| Novex-2 | 15705 | 47338;47339;47340 | chr2:178572400;178572399;178572398 | chr2:179437127;179437126;179437125 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/C | rs753105114  |
None | 1.0 | N | 0.761 | 0.363 | 0.224531998449 | 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 |
| W/C | rs753105114 |
None | 1.0 | N | 0.761 | 0.363 | 0.224531998449 | gnomAD-4.0.0 | 6.84538E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99875E-07 | 0 | 0 |
| W/R | rs1276766342 |
-1.582 | 0.999 | N | 0.778 | 0.485 | 0.59874208065 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| W/R | rs1276766342 |
-1.582 | 0.999 | N | 0.778 | 0.485 | 0.59874208065 | 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 |
| W/R | rs1276766342 |
-1.582 | 0.999 | N | 0.778 | 0.485 | 0.59874208065 | gnomAD-4.0.0 | 2.56448E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.79196E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/A | 0.7609 | likely_pathogenic | 0.6912 | pathogenic | -2.629 | Highly Destabilizing | 0.979 | D | 0.691 | prob.neutral | None | None | None | None | N |
| W/C | 0.6317 | likely_pathogenic | 0.5724 | pathogenic | -1.564 | Destabilizing | 1.0 | D | 0.761 | deleterious | N | 0.415218361 | None | None | N |
| W/D | 0.9856 | likely_pathogenic | 0.9784 | pathogenic | -1.665 | Destabilizing | 0.999 | D | 0.78 | deleterious | None | None | None | None | N |
| W/E | 0.9714 | likely_pathogenic | 0.9634 | pathogenic | -1.553 | Destabilizing | 0.999 | D | 0.772 | deleterious | None | None | None | None | N |
| W/F | 0.1582 | likely_benign | 0.171 | benign | -1.429 | Destabilizing | 0.98 | D | 0.628 | neutral | None | None | None | None | N |
| W/G | 0.7023 | likely_pathogenic | 0.629 | pathogenic | -2.863 | Highly Destabilizing | 0.996 | D | 0.677 | prob.neutral | N | 0.509205958 | None | None | N |
| W/H | 0.8134 | likely_pathogenic | 0.8093 | pathogenic | -1.445 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| W/I | 0.6057 | likely_pathogenic | 0.5579 | ambiguous | -1.787 | Destabilizing | 0.256 | N | 0.554 | neutral | None | None | None | None | N |
| W/K | 0.9558 | likely_pathogenic | 0.9494 | pathogenic | -2.003 | Highly Destabilizing | 0.997 | D | 0.771 | deleterious | None | None | None | None | N |
| W/L | 0.3818 | ambiguous | 0.3791 | ambiguous | -1.787 | Destabilizing | 0.861 | D | 0.614 | neutral | N | 0.435668204 | None | None | N |
| W/M | 0.6143 | likely_pathogenic | 0.6003 | pathogenic | -1.416 | Destabilizing | 0.998 | D | 0.739 | prob.delet. | None | None | None | None | N |
| W/N | 0.9567 | likely_pathogenic | 0.9395 | pathogenic | -2.551 | Highly Destabilizing | 0.999 | D | 0.771 | deleterious | None | None | None | None | N |
| W/P | 0.9969 | likely_pathogenic | 0.9947 | pathogenic | -2.087 | Highly Destabilizing | 0.999 | D | 0.773 | deleterious | None | None | None | None | N |
| W/Q | 0.9273 | likely_pathogenic | 0.912 | pathogenic | -2.357 | Highly Destabilizing | 0.999 | D | 0.775 | deleterious | None | None | None | None | N |
| W/R | 0.9228 | likely_pathogenic | 0.9076 | pathogenic | -1.728 | Destabilizing | 0.999 | D | 0.778 | deleterious | N | 0.481951395 | None | None | N |
| W/S | 0.7355 | likely_pathogenic | 0.6561 | pathogenic | -2.914 | Highly Destabilizing | 0.996 | D | 0.769 | deleterious | N | 0.500047757 | None | None | N |
| W/T | 0.8178 | likely_pathogenic | 0.7572 | pathogenic | -2.752 | Highly Destabilizing | 0.994 | D | 0.694 | prob.neutral | None | None | None | None | N |
| W/V | 0.5314 | ambiguous | 0.4818 | ambiguous | -2.087 | Highly Destabilizing | 0.891 | D | 0.645 | neutral | None | None | None | None | N |
| W/Y | 0.3679 | ambiguous | 0.3669 | ambiguous | -1.35 | Destabilizing | 0.99 | D | 0.629 | 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.