Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1342 | 4249;4250;4251 | chr2:178779058;178779057;178779056 | chr2:179643785;179643784;179643783 |
| N2AB | 1342 | 4249;4250;4251 | chr2:178779058;178779057;178779056 | chr2:179643785;179643784;179643783 |
| N2A | 1342 | 4249;4250;4251 | chr2:178779058;178779057;178779056 | chr2:179643785;179643784;179643783 |
| N2B | 1296 | 4111;4112;4113 | chr2:178779058;178779057;178779056 | chr2:179643785;179643784;179643783 |
| Novex-1 | 1296 | 4111;4112;4113 | chr2:178779058;178779057;178779056 | chr2:179643785;179643784;179643783 |
| Novex-2 | 1296 | 4111;4112;4113 | chr2:178779058;178779057;178779056 | chr2:179643785;179643784;179643783 |
| Novex-3 | 1342 | 4249;4250;4251 | chr2:178779058;178779057;178779056 | chr2:179643785;179643784;179643783 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | rs1561323110  |
None | 1.0 | N | 0.739 | 0.62 | 0.852661866299 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/P | rs1561323110 |
None | 1.0 | N | 0.739 | 0.62 | 0.852661866299 | gnomAD-4.0.0 | 1.36828E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99339E-07 | 0 | 1.65596E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.5152 | ambiguous | 0.4675 | ambiguous | -1.076 | Destabilizing | 0.998 | D | 0.517 | neutral | None | None | None | None | I |
| L/C | 0.8014 | likely_pathogenic | 0.7662 | pathogenic | -0.634 | Destabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | I |
| L/D | 0.8929 | likely_pathogenic | 0.8646 | pathogenic | -0.34 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | I |
| L/E | 0.6352 | likely_pathogenic | 0.5867 | pathogenic | -0.387 | Destabilizing | 0.999 | D | 0.731 | prob.delet. | None | None | None | None | I |
| L/F | 0.2786 | likely_benign | 0.2434 | benign | -0.812 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | I |
| L/G | 0.7399 | likely_pathogenic | 0.6944 | pathogenic | -1.324 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| L/H | 0.4022 | ambiguous | 0.3497 | ambiguous | -0.505 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| L/I | 0.24 | likely_benign | 0.2284 | benign | -0.51 | Destabilizing | 0.999 | D | 0.435 | neutral | N | 0.500933146 | None | None | I |
| L/K | 0.5504 | ambiguous | 0.5014 | ambiguous | -0.61 | Destabilizing | 0.998 | D | 0.643 | neutral | None | None | None | None | I |
| L/M | 0.2091 | likely_benign | 0.1936 | benign | -0.435 | Destabilizing | 1.0 | D | 0.619 | neutral | None | None | None | None | I |
| L/N | 0.6148 | likely_pathogenic | 0.5605 | ambiguous | -0.369 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| L/P | 0.8801 | likely_pathogenic | 0.8769 | pathogenic | -0.665 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.50414849 | None | None | I |
| L/Q | 0.246 | likely_benign | 0.2157 | benign | -0.566 | Destabilizing | 0.999 | D | 0.726 | prob.delet. | N | 0.500232091 | None | None | I |
| L/R | 0.4124 | ambiguous | 0.3781 | ambiguous | -0.031 | Destabilizing | 0.64 | D | 0.367 | neutral | N | 0.501278926 | None | None | I |
| L/S | 0.4575 | ambiguous | 0.3966 | ambiguous | -0.926 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | I |
| L/T | 0.4194 | ambiguous | 0.3774 | ambiguous | -0.858 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| L/V | 0.2504 | likely_benign | 0.236 | benign | -0.665 | Destabilizing | 0.998 | D | 0.437 | neutral | N | 0.502469275 | None | None | I |
| L/W | 0.6017 | likely_pathogenic | 0.573 | pathogenic | -0.836 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | I |
| L/Y | 0.6396 | likely_pathogenic | 0.5901 | pathogenic | -0.607 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | 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.