Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14285 | 43078;43079;43080 | chr2:178633506;178633505;178633504 | chr2:179498233;179498232;179498231 |
| N2AB | 12644 | 38155;38156;38157 | chr2:178633506;178633505;178633504 | chr2:179498233;179498232;179498231 |
| N2A | 11717 | 35374;35375;35376 | chr2:178633506;178633505;178633504 | chr2:179498233;179498232;179498231 |
| N2B | 5220 | 15883;15884;15885 | chr2:178633506;178633505;178633504 | chr2:179498233;179498232;179498231 |
| Novex-1 | 5345 | 16258;16259;16260 | chr2:178633506;178633505;178633504 | chr2:179498233;179498232;179498231 |
| Novex-2 | 5412 | 16459;16460;16461 | chr2:178633506;178633505;178633504 | chr2:179498233;179498232;179498231 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | None | None | 0.998 | N | 0.533 | 0.225 | 0.533614126537 | gnomAD-4.0.0 | 1.59229E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8595E-06 | 0 | 0 |
| I/M | rs761517606  |
None | 0.998 | N | 0.531 | 0.224 | 0.471700387322 | gnomAD-4.0.0 | 1.3688E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79918E-06 | 0 | 0 |
| I/N | None | None | 0.988 | N | 0.62 | 0.261 | 0.833390104951 | gnomAD-4.0.0 | 1.36879E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79918E-06 | 0 | 0 |
| I/V | rs771436214 |
-1.479 | 0.906 | N | 0.453 | 0.108 | 0.597979452267 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 8.7E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs771436214 |
-1.479 | 0.906 | N | 0.453 | 0.108 | 0.597979452267 | gnomAD-4.0.0 | 4.77686E-06 | None | None | None | None | N | None | 0 | 6.86405E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4618 | ambiguous | 0.3179 | benign | -2.81 | Highly Destabilizing | 0.864 | D | 0.481 | neutral | None | None | None | None | N |
| I/C | 0.7298 | likely_pathogenic | 0.6381 | pathogenic | -1.883 | Destabilizing | 1.0 | D | 0.539 | neutral | None | None | None | None | N |
| I/D | 0.7045 | likely_pathogenic | 0.5852 | pathogenic | -3.221 | Highly Destabilizing | 0.991 | D | 0.621 | neutral | None | None | None | None | N |
| I/E | 0.5117 | ambiguous | 0.4421 | ambiguous | -3.009 | Highly Destabilizing | 0.991 | D | 0.616 | neutral | None | None | None | None | N |
| I/F | 0.1663 | likely_benign | 0.1346 | benign | -1.682 | Destabilizing | 0.998 | D | 0.533 | neutral | N | 0.501156472 | None | None | N |
| I/G | 0.7265 | likely_pathogenic | 0.5723 | pathogenic | -3.331 | Highly Destabilizing | 0.969 | D | 0.578 | neutral | None | None | None | None | N |
| I/H | 0.4415 | ambiguous | 0.3775 | ambiguous | -2.763 | Highly Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | N |
| I/K | 0.4741 | ambiguous | 0.3867 | ambiguous | -2.221 | Highly Destabilizing | 0.991 | D | 0.62 | neutral | None | None | None | None | N |
| I/L | 0.1619 | likely_benign | 0.1213 | benign | -1.289 | Destabilizing | 0.906 | D | 0.471 | neutral | N | 0.508462742 | None | None | N |
| I/M | 0.1291 | likely_benign | 0.1064 | benign | -1.101 | Destabilizing | 0.998 | D | 0.531 | neutral | N | 0.501858903 | None | None | N |
| I/N | 0.2539 | likely_benign | 0.1706 | benign | -2.507 | Highly Destabilizing | 0.988 | D | 0.62 | neutral | N | 0.507795677 | None | None | N |
| I/P | 0.9778 | likely_pathogenic | 0.9431 | pathogenic | -1.78 | Destabilizing | 0.995 | D | 0.641 | neutral | None | None | None | None | N |
| I/Q | 0.4292 | ambiguous | 0.3683 | ambiguous | -2.399 | Highly Destabilizing | 0.995 | D | 0.649 | neutral | None | None | None | None | N |
| I/R | 0.4274 | ambiguous | 0.3185 | benign | -1.833 | Destabilizing | 0.995 | D | 0.642 | neutral | None | None | None | None | N |
| I/S | 0.2802 | likely_benign | 0.1935 | benign | -3.154 | Highly Destabilizing | 0.476 | N | 0.471 | neutral | N | 0.438202104 | None | None | N |
| I/T | 0.2469 | likely_benign | 0.1533 | benign | -2.815 | Highly Destabilizing | 0.116 | N | 0.307 | neutral | N | 0.479881812 | None | None | N |
| I/V | 0.1083 | likely_benign | 0.0812 | benign | -1.78 | Destabilizing | 0.906 | D | 0.453 | neutral | N | 0.508916419 | None | None | N |
| I/W | 0.7134 | likely_pathogenic | 0.6942 | pathogenic | -2.128 | Highly Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| I/Y | 0.3866 | ambiguous | 0.3534 | ambiguous | -1.895 | Destabilizing | 0.999 | D | 0.555 | 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.