Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16999 | 51220;51221;51222 | chr2:178611134;178611133;178611132 | chr2:179475861;179475860;179475859 |
| N2AB | 15358 | 46297;46298;46299 | chr2:178611134;178611133;178611132 | chr2:179475861;179475860;179475859 |
| N2A | 14431 | 43516;43517;43518 | chr2:178611134;178611133;178611132 | chr2:179475861;179475860;179475859 |
| N2B | 7934 | 24025;24026;24027 | chr2:178611134;178611133;178611132 | chr2:179475861;179475860;179475859 |
| Novex-1 | 8059 | 24400;24401;24402 | chr2:178611134;178611133;178611132 | chr2:179475861;179475860;179475859 |
| Novex-2 | 8126 | 24601;24602;24603 | chr2:178611134;178611133;178611132 | chr2:179475861;179475860;179475859 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 0.767 | N | 0.333 | 0.186 | 0.0986583533028 | gnomAD-4.0.0 | 6.84573E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99839E-07 | 0 | 0 |
| D/G | rs1576414391  |
None | 0.998 | N | 0.547 | 0.459 | 0.17258766438 | gnomAD-4.0.0 | 1.36915E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.05766E-05 | None | 0 | 0 | 0 | 0 | 0 |
| D/V | None | None | 0.999 | D | 0.655 | 0.529 | 0.535726849619 | gnomAD-4.0.0 | 6.84573E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99842E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1728 | likely_benign | 0.2092 | benign | 0.092 | Stabilizing | 0.999 | D | 0.511 | neutral | N | 0.450743919 | None | None | N |
| D/C | 0.6004 | likely_pathogenic | 0.6733 | pathogenic | -0.127 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| D/E | 0.124 | likely_benign | 0.1464 | benign | -0.422 | Destabilizing | 0.767 | D | 0.333 | neutral | N | 0.447911905 | None | None | N |
| D/F | 0.6459 | likely_pathogenic | 0.7268 | pathogenic | -0.108 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| D/G | 0.149 | likely_benign | 0.181 | benign | 0.023 | Stabilizing | 0.998 | D | 0.547 | neutral | N | 0.446911019 | None | None | N |
| D/H | 0.2824 | likely_benign | 0.3559 | ambiguous | 0.501 | Stabilizing | 1.0 | D | 0.654 | neutral | N | 0.448274022 | None | None | N |
| D/I | 0.4028 | ambiguous | 0.4927 | ambiguous | 0.2 | Stabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| D/K | 0.2997 | likely_benign | 0.3868 | ambiguous | 0.395 | Stabilizing | 0.999 | D | 0.569 | neutral | None | None | None | None | N |
| D/L | 0.386 | ambiguous | 0.457 | ambiguous | 0.2 | Stabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| D/M | 0.619 | likely_pathogenic | 0.6977 | pathogenic | 0.013 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/N | 0.1108 | likely_benign | 0.1372 | benign | 0.265 | Stabilizing | 0.999 | D | 0.639 | neutral | N | 0.440930332 | None | None | N |
| D/P | 0.4514 | ambiguous | 0.4923 | ambiguous | 0.18 | Stabilizing | 1.0 | D | 0.611 | neutral | None | None | None | None | N |
| D/Q | 0.293 | likely_benign | 0.3582 | ambiguous | 0.241 | Stabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | N |
| D/R | 0.3808 | ambiguous | 0.4573 | ambiguous | 0.547 | Stabilizing | 0.999 | D | 0.614 | neutral | None | None | None | None | N |
| D/S | 0.1194 | likely_benign | 0.1463 | benign | 0.167 | Stabilizing | 0.997 | D | 0.567 | neutral | None | None | None | None | N |
| D/T | 0.2455 | likely_benign | 0.301 | benign | 0.227 | Stabilizing | 1.0 | D | 0.598 | neutral | None | None | None | None | N |
| D/V | 0.2457 | likely_benign | 0.2988 | benign | 0.18 | Stabilizing | 0.999 | D | 0.655 | neutral | D | 0.576718186 | None | None | N |
| D/W | 0.8752 | likely_pathogenic | 0.9015 | pathogenic | -0.124 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| D/Y | 0.2954 | likely_benign | 0.3615 | ambiguous | 0.098 | Stabilizing | 1.0 | D | 0.674 | neutral | D | 0.575642468 | 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.