Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17838 | 53737;53738;53739 | chr2:178607090;178607089;178607088 | chr2:179471817;179471816;179471815 |
| N2AB | 16197 | 48814;48815;48816 | chr2:178607090;178607089;178607088 | chr2:179471817;179471816;179471815 |
| N2A | 15270 | 46033;46034;46035 | chr2:178607090;178607089;178607088 | chr2:179471817;179471816;179471815 |
| N2B | 8773 | 26542;26543;26544 | chr2:178607090;178607089;178607088 | chr2:179471817;179471816;179471815 |
| Novex-1 | 8898 | 26917;26918;26919 | chr2:178607090;178607089;178607088 | chr2:179471817;179471816;179471815 |
| Novex-2 | 8965 | 27118;27119;27120 | chr2:178607090;178607089;178607088 | chr2:179471817;179471816;179471815 |
| 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/T | None | None | 0.001 | N | 0.403 | 0.121 | 0.456919554969 | gnomAD-4.0.0 | 1.59447E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86297E-06 | 0 | 0 |
| I/V | rs1339075657  |
-1.716 | None | N | 0.115 | 0.131 | 0.318828661733 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| I/V | rs1339075657 |
-1.716 | None | N | 0.115 | 0.131 | 0.318828661733 | gnomAD-4.0.0 | 1.59448E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86302E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3961 | ambiguous | 0.3483 | ambiguous | -2.87 | Highly Destabilizing | 0.025 | N | 0.545 | neutral | None | None | None | None | N |
| I/C | 0.6826 | likely_pathogenic | 0.6775 | pathogenic | -2.032 | Highly Destabilizing | 0.002 | N | 0.538 | neutral | None | None | None | None | N |
| I/D | 0.9678 | likely_pathogenic | 0.9515 | pathogenic | -3.361 | Highly Destabilizing | 0.22 | N | 0.687 | prob.neutral | None | None | None | None | N |
| I/E | 0.8817 | likely_pathogenic | 0.8355 | pathogenic | -3.17 | Highly Destabilizing | 0.22 | N | 0.661 | neutral | None | None | None | None | N |
| I/F | 0.3457 | ambiguous | 0.2984 | benign | -1.709 | Destabilizing | None | N | 0.2 | neutral | N | 0.462492233 | None | None | N |
| I/G | 0.8772 | likely_pathogenic | 0.8593 | pathogenic | -3.341 | Highly Destabilizing | 0.124 | N | 0.647 | neutral | None | None | None | None | N |
| I/H | 0.8466 | likely_pathogenic | 0.789 | pathogenic | -2.734 | Highly Destabilizing | 0.859 | D | 0.665 | neutral | None | None | None | None | N |
| I/K | 0.799 | likely_pathogenic | 0.7255 | pathogenic | -2.341 | Highly Destabilizing | 0.22 | N | 0.658 | neutral | None | None | None | None | N |
| I/L | 0.2114 | likely_benign | 0.1956 | benign | -1.5 | Destabilizing | 0.019 | N | 0.334 | neutral | N | 0.493313785 | None | None | N |
| I/M | 0.13 | likely_benign | 0.1087 | benign | -1.42 | Destabilizing | 0.427 | N | 0.571 | neutral | N | 0.479173839 | None | None | N |
| I/N | 0.7239 | likely_pathogenic | 0.6056 | pathogenic | -2.598 | Highly Destabilizing | 0.427 | N | 0.682 | prob.neutral | N | 0.471355558 | None | None | N |
| I/P | 0.993 | likely_pathogenic | 0.9928 | pathogenic | -1.942 | Destabilizing | 0.667 | D | 0.69 | prob.neutral | None | None | None | None | N |
| I/Q | 0.7473 | likely_pathogenic | 0.6732 | pathogenic | -2.52 | Highly Destabilizing | 0.667 | D | 0.671 | neutral | None | None | None | None | N |
| I/R | 0.6949 | likely_pathogenic | 0.6043 | pathogenic | -1.879 | Destabilizing | 0.497 | N | 0.686 | prob.neutral | None | None | None | None | N |
| I/S | 0.431 | ambiguous | 0.3296 | benign | -3.187 | Highly Destabilizing | 0.003 | N | 0.516 | neutral | N | 0.450120369 | None | None | N |
| I/T | 0.2149 | likely_benign | 0.1618 | benign | -2.885 | Highly Destabilizing | 0.001 | N | 0.403 | neutral | N | 0.439191299 | None | None | N |
| I/V | 0.0979 | likely_benign | 0.0956 | benign | -1.942 | Destabilizing | None | N | 0.115 | neutral | N | 0.435593633 | None | None | N |
| I/W | 0.9095 | likely_pathogenic | 0.8989 | pathogenic | -2.116 | Highly Destabilizing | 0.958 | D | 0.681 | prob.neutral | None | None | None | None | N |
| I/Y | 0.7838 | likely_pathogenic | 0.7259 | pathogenic | -1.924 | Destabilizing | 0.124 | N | 0.676 | prob.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.