Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2974 | 9145;9146;9147 | chr2:178768916;178768915;178768914 | chr2:179633643;179633642;179633641 |
| N2AB | 2974 | 9145;9146;9147 | chr2:178768916;178768915;178768914 | chr2:179633643;179633642;179633641 |
| N2A | 2974 | 9145;9146;9147 | chr2:178768916;178768915;178768914 | chr2:179633643;179633642;179633641 |
| N2B | 2928 | 9007;9008;9009 | chr2:178768916;178768915;178768914 | chr2:179633643;179633642;179633641 |
| Novex-1 | 2928 | 9007;9008;9009 | chr2:178768916;178768915;178768914 | chr2:179633643;179633642;179633641 |
| Novex-2 | 2928 | 9007;9008;9009 | chr2:178768916;178768915;178768914 | chr2:179633643;179633642;179633641 |
| Novex-3 | 2974 | 9145;9146;9147 | chr2:178768916;178768915;178768914 | chr2:179633643;179633642;179633641 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/T | rs899464143  |
0.718 | 0.994 | N | 0.625 | 0.511 | 0.826595815848 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.76E-05 | 0 |
| M/T | rs899464143 |
0.718 | 0.994 | N | 0.625 | 0.511 | 0.826595815848 | gnomAD-4.0.0 | 7.52596E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 8.67152E-04 | 3.59723E-06 | 0 | 3.31192E-05 |
| M/V | rs993689796 |
None | 0.985 | N | 0.439 | 0.371 | 0.554156219314 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5496 | ambiguous | 0.5145 | ambiguous | -0.292 | Destabilizing | 0.989 | D | 0.625 | neutral | None | None | None | None | N |
| M/C | 0.8971 | likely_pathogenic | 0.9101 | pathogenic | -0.503 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | N |
| M/D | 0.9069 | likely_pathogenic | 0.8995 | pathogenic | 0.851 | Stabilizing | 0.999 | D | 0.69 | prob.neutral | None | None | None | None | N |
| M/E | 0.6859 | likely_pathogenic | 0.6683 | pathogenic | 0.825 | Stabilizing | 0.999 | D | 0.607 | neutral | None | None | None | None | N |
| M/F | 0.5114 | ambiguous | 0.54 | ambiguous | 0.197 | Stabilizing | 0.999 | D | 0.576 | neutral | None | None | None | None | N |
| M/G | 0.8391 | likely_pathogenic | 0.8103 | pathogenic | -0.503 | Destabilizing | 0.995 | D | 0.623 | neutral | None | None | None | None | N |
| M/H | 0.7204 | likely_pathogenic | 0.7284 | pathogenic | 0.272 | Stabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| M/I | 0.6041 | likely_pathogenic | 0.595 | pathogenic | 0.172 | Stabilizing | 0.985 | D | 0.625 | neutral | N | 0.494764114 | None | None | N |
| M/K | 0.3453 | ambiguous | 0.3445 | ambiguous | 0.651 | Stabilizing | 0.994 | D | 0.631 | neutral | N | 0.475509879 | None | None | N |
| M/L | 0.1843 | likely_benign | 0.1721 | benign | 0.172 | Stabilizing | 0.927 | D | 0.232 | neutral | N | 0.501486827 | None | None | N |
| M/N | 0.7079 | likely_pathogenic | 0.6937 | pathogenic | 0.719 | Stabilizing | 0.999 | D | 0.69 | prob.neutral | None | None | None | None | N |
| M/P | 0.6481 | likely_pathogenic | 0.6081 | pathogenic | 0.048 | Stabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | N |
| M/Q | 0.4201 | ambiguous | 0.3993 | ambiguous | 0.636 | Stabilizing | 0.999 | D | 0.569 | neutral | None | None | None | None | N |
| M/R | 0.3801 | ambiguous | 0.3667 | ambiguous | 0.979 | Stabilizing | 0.998 | D | 0.616 | neutral | N | 0.477944572 | None | None | N |
| M/S | 0.6066 | likely_pathogenic | 0.5842 | pathogenic | 0.172 | Stabilizing | 0.995 | D | 0.599 | neutral | None | None | None | None | N |
| M/T | 0.4081 | ambiguous | 0.3607 | ambiguous | 0.263 | Stabilizing | 0.994 | D | 0.625 | neutral | N | 0.496622385 | None | None | N |
| M/V | 0.1468 | likely_benign | 0.1361 | benign | 0.048 | Stabilizing | 0.985 | D | 0.439 | neutral | N | 0.4962029 | None | None | N |
| M/W | 0.8719 | likely_pathogenic | 0.8695 | pathogenic | 0.183 | Stabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | N |
| M/Y | 0.7764 | likely_pathogenic | 0.7974 | pathogenic | 0.365 | Stabilizing | 0.999 | D | 0.663 | 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.