Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25201 | 75826;75827;75828 | chr2:178570531;178570530;178570529 | chr2:179435258;179435257;179435256 |
| N2AB | 23560 | 70903;70904;70905 | chr2:178570531;178570530;178570529 | chr2:179435258;179435257;179435256 |
| N2A | 22633 | 68122;68123;68124 | chr2:178570531;178570530;178570529 | chr2:179435258;179435257;179435256 |
| N2B | 16136 | 48631;48632;48633 | chr2:178570531;178570530;178570529 | chr2:179435258;179435257;179435256 |
| Novex-1 | 16261 | 49006;49007;49008 | chr2:178570531;178570530;178570529 | chr2:179435258;179435257;179435256 |
| Novex-2 | 16328 | 49207;49208;49209 | chr2:178570531;178570530;178570529 | chr2:179435258;179435257;179435256 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/G | rs774448134  |
-0.958 | 1.0 | D | 0.825 | 0.879 | 0.919655124817 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66611E-04 |
| V/G | rs774448134 |
-0.958 | 1.0 | D | 0.825 | 0.879 | 0.919655124817 | gnomAD-4.0.0 | 1.59235E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02663E-05 |
| V/I | rs1707800983 |
None | 0.997 | D | 0.767 | 0.51 | 0.82295470488 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs1707800983 |
None | 0.997 | D | 0.767 | 0.51 | 0.82295470488 | gnomAD-4.0.0 | 2.03008E-06 | None | None | None | None | I | None | 1.74764E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.20499E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.9601 | likely_pathogenic | 0.9605 | pathogenic | -1.971 | Destabilizing | 0.999 | D | 0.819 | deleterious | D | 0.607142267 | None | None | I |
| V/C | 0.9847 | likely_pathogenic | 0.9869 | pathogenic | -1.665 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | I |
| V/D | 0.9985 | likely_pathogenic | 0.9981 | pathogenic | -2.432 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | D | 0.639786402 | None | None | I |
| V/E | 0.9958 | likely_pathogenic | 0.9954 | pathogenic | -2.365 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | I |
| V/F | 0.9599 | likely_pathogenic | 0.9638 | pathogenic | -1.427 | Destabilizing | 1.0 | D | 0.876 | deleterious | D | 0.639180989 | None | None | I |
| V/G | 0.9655 | likely_pathogenic | 0.9636 | pathogenic | -2.356 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | D | 0.639786402 | None | None | I |
| V/H | 0.9987 | likely_pathogenic | 0.9988 | pathogenic | -1.893 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | I |
| V/I | 0.1462 | likely_benign | 0.1395 | benign | -0.963 | Destabilizing | 0.997 | D | 0.767 | deleterious | D | 0.523690444 | None | None | I |
| V/K | 0.9972 | likely_pathogenic | 0.9972 | pathogenic | -1.691 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | I |
| V/L | 0.927 | likely_pathogenic | 0.9276 | pathogenic | -0.963 | Destabilizing | 0.997 | D | 0.82 | deleterious | D | 0.611624835 | None | None | I |
| V/M | 0.9274 | likely_pathogenic | 0.9343 | pathogenic | -0.901 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | I |
| V/N | 0.9931 | likely_pathogenic | 0.9923 | pathogenic | -1.693 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | I |
| V/P | 0.9933 | likely_pathogenic | 0.9932 | pathogenic | -1.268 | Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | I |
| V/Q | 0.9968 | likely_pathogenic | 0.9969 | pathogenic | -1.808 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | I |
| V/R | 0.9946 | likely_pathogenic | 0.9948 | pathogenic | -1.211 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | I |
| V/S | 0.982 | likely_pathogenic | 0.9815 | pathogenic | -2.239 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | I |
| V/T | 0.9633 | likely_pathogenic | 0.9628 | pathogenic | -2.059 | Highly Destabilizing | 0.999 | D | 0.862 | deleterious | None | None | None | None | I |
| V/W | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -1.717 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | I |
| V/Y | 0.9943 | likely_pathogenic | 0.9951 | pathogenic | -1.427 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | I |
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.