Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18311 | 55156;55157;55158 | chr2:178602471;178602470;178602469 | chr2:179467198;179467197;179467196 |
| N2AB | 16670 | 50233;50234;50235 | chr2:178602471;178602470;178602469 | chr2:179467198;179467197;179467196 |
| N2A | 15743 | 47452;47453;47454 | chr2:178602471;178602470;178602469 | chr2:179467198;179467197;179467196 |
| N2B | 9246 | 27961;27962;27963 | chr2:178602471;178602470;178602469 | chr2:179467198;179467197;179467196 |
| Novex-1 | 9371 | 28336;28337;28338 | chr2:178602471;178602470;178602469 | chr2:179467198;179467197;179467196 |
| Novex-2 | 9438 | 28537;28538;28539 | chr2:178602471;178602470;178602469 | chr2:179467198;179467197;179467196 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs564906146  |
0.531 | 0.021 | N | 0.259 | 0.16 | 0.402899589544 | gnomAD-2.1.1 | 7.89E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54707E-04 | None | 0 | 0 | 2.82965E-04 |
| M/I | rs564906146 |
0.531 | 0.021 | N | 0.259 | 0.16 | 0.402899589544 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 6.21118E-04 | 0 |
| M/I | rs564906146 |
0.531 | 0.021 | N | 0.259 | 0.16 | 0.402899589544 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| M/I | rs564906146 |
0.531 | 0.021 | N | 0.259 | 0.16 | 0.402899589544 | gnomAD-4.0.0 | 3.84566E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.65453E-04 | 8.48145E-07 | 6.15452E-04 | 6.41067E-05 |
| M/T | rs1553676016 |
None | 0.959 | N | 0.662 | 0.37 | 0.602267601113 | gnomAD-4.0.0 | 1.59477E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.03122E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.716 | likely_pathogenic | 0.6868 | pathogenic | -2.115 | Highly Destabilizing | 0.863 | D | 0.584 | neutral | None | None | None | None | N |
| M/C | 0.6383 | likely_pathogenic | 0.6491 | pathogenic | -1.961 | Destabilizing | 0.997 | D | 0.714 | prob.delet. | None | None | None | None | N |
| M/D | 0.9814 | likely_pathogenic | 0.9854 | pathogenic | -1.94 | Destabilizing | 0.997 | D | 0.729 | prob.delet. | None | None | None | None | N |
| M/E | 0.7901 | likely_pathogenic | 0.8133 | pathogenic | -1.687 | Destabilizing | 0.99 | D | 0.675 | prob.neutral | None | None | None | None | N |
| M/F | 0.3457 | ambiguous | 0.2852 | benign | -0.734 | Destabilizing | 0.969 | D | 0.665 | neutral | None | None | None | None | N |
| M/G | 0.8684 | likely_pathogenic | 0.8651 | pathogenic | -2.606 | Highly Destabilizing | 0.99 | D | 0.669 | neutral | None | None | None | None | N |
| M/H | 0.7612 | likely_pathogenic | 0.7439 | pathogenic | -2.241 | Highly Destabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | N |
| M/I | 0.4385 | ambiguous | 0.4031 | ambiguous | -0.69 | Destabilizing | 0.021 | N | 0.259 | neutral | N | 0.419720104 | None | None | N |
| M/K | 0.3708 | ambiguous | 0.3265 | benign | -1.211 | Destabilizing | 0.986 | D | 0.661 | neutral | N | 0.364674898 | None | None | N |
| M/L | 0.2045 | likely_benign | 0.1966 | benign | -0.69 | Destabilizing | 0.31 | N | 0.336 | neutral | N | 0.454061964 | None | None | N |
| M/N | 0.8592 | likely_pathogenic | 0.8719 | pathogenic | -1.675 | Destabilizing | 0.997 | D | 0.697 | prob.neutral | None | None | None | None | N |
| M/P | 0.9975 | likely_pathogenic | 0.9984 | pathogenic | -1.149 | Destabilizing | 0.997 | D | 0.697 | prob.neutral | None | None | None | None | N |
| M/Q | 0.4724 | ambiguous | 0.4533 | ambiguous | -1.329 | Destabilizing | 0.997 | D | 0.694 | prob.neutral | None | None | None | None | N |
| M/R | 0.4454 | ambiguous | 0.4173 | ambiguous | -1.382 | Destabilizing | 0.996 | D | 0.697 | prob.neutral | N | 0.380548427 | None | None | N |
| M/S | 0.746 | likely_pathogenic | 0.7224 | pathogenic | -2.208 | Highly Destabilizing | 0.99 | D | 0.661 | neutral | None | None | None | None | N |
| M/T | 0.5561 | ambiguous | 0.5443 | ambiguous | -1.822 | Destabilizing | 0.959 | D | 0.662 | neutral | N | 0.478152332 | None | None | N |
| M/V | 0.156 | likely_benign | 0.1566 | benign | -1.149 | Destabilizing | 0.31 | N | 0.463 | neutral | N | 0.430089026 | None | None | N |
| M/W | 0.7069 | likely_pathogenic | 0.6844 | pathogenic | -1.071 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | None | None | None | None | N |
| M/Y | 0.5548 | ambiguous | 0.4764 | ambiguous | -1.018 | Destabilizing | 0.997 | D | 0.707 | 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.