Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33091 | 99496;99497;99498 | chr2:178538558;178538557;178538556 | chr2:179403285;179403284;179403283 |
| N2AB | 31450 | 94573;94574;94575 | chr2:178538558;178538557;178538556 | chr2:179403285;179403284;179403283 |
| N2A | 30523 | 91792;91793;91794 | chr2:178538558;178538557;178538556 | chr2:179403285;179403284;179403283 |
| N2B | 24026 | 72301;72302;72303 | chr2:178538558;178538557;178538556 | chr2:179403285;179403284;179403283 |
| Novex-1 | 24151 | 72676;72677;72678 | chr2:178538558;178538557;178538556 | chr2:179403285;179403284;179403283 |
| Novex-2 | 24218 | 72877;72878;72879 | chr2:178538558;178538557;178538556 | chr2:179403285;179403284;179403283 |
| 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/L | rs879450752  |
None | 0.012 | D | 0.399 | 0.176 | 0.18995819373 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/L | rs879450752 |
None | 0.012 | D | 0.399 | 0.176 | 0.18995819373 | gnomAD-4.0.0 | 4.96205E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.78507E-06 | 0 | 0 |
| I/M | rs746305727 |
None | 0.314 | N | 0.732 | 0.136 | 0.557953424633 | gnomAD-4.0.0 | 1.23297E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.62022E-05 | 0 | 0 |
| I/R | None | None | 0.481 | N | 0.868 | 0.366 | 0.805266226371 | gnomAD-4.0.0 | 1.59537E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77423E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs879450752 |
None | None | N | 0.173 | 0.175 | 0.156986980423 | gnomAD-4.0.0 | 6.84925E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00066E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4171 | ambiguous | 0.4146 | ambiguous | -2.15 | Highly Destabilizing | 0.034 | N | 0.686 | prob.delet. | None | None | None | None | N |
| I/C | 0.6817 | likely_pathogenic | 0.6633 | pathogenic | -1.549 | Destabilizing | 0.823 | D | 0.727 | deleterious | None | None | None | None | N |
| I/D | 0.9228 | likely_pathogenic | 0.9137 | pathogenic | -1.769 | Destabilizing | 0.552 | D | 0.873 | deleterious | None | None | None | None | N |
| I/E | 0.8264 | likely_pathogenic | 0.8041 | pathogenic | -1.578 | Destabilizing | 0.552 | D | 0.832 | deleterious | None | None | None | None | N |
| I/F | 0.1918 | likely_benign | 0.1827 | benign | -1.2 | Destabilizing | 0.378 | N | 0.74 | deleterious | None | None | None | None | N |
| I/G | 0.7352 | likely_pathogenic | 0.7433 | pathogenic | -2.637 | Highly Destabilizing | 0.552 | D | 0.778 | deleterious | None | None | None | None | N |
| I/H | 0.7908 | likely_pathogenic | 0.7236 | pathogenic | -1.683 | Destabilizing | 0.934 | D | 0.861 | deleterious | None | None | None | None | N |
| I/K | 0.7589 | likely_pathogenic | 0.7055 | pathogenic | -1.594 | Destabilizing | 0.481 | N | 0.834 | deleterious | N | 0.488793428 | None | None | N |
| I/L | 0.1352 | likely_benign | 0.1404 | benign | -0.775 | Destabilizing | 0.012 | N | 0.399 | neutral | D | 0.527205433 | None | None | N |
| I/M | 0.1261 | likely_benign | 0.127 | benign | -0.8 | Destabilizing | 0.314 | N | 0.732 | deleterious | N | 0.488793428 | None | None | N |
| I/N | 0.617 | likely_pathogenic | 0.5669 | pathogenic | -1.861 | Destabilizing | 0.789 | D | 0.869 | deleterious | None | None | None | None | N |
| I/P | 0.9357 | likely_pathogenic | 0.9263 | pathogenic | -1.211 | Destabilizing | 0.789 | D | 0.872 | deleterious | None | None | None | None | N |
| I/Q | 0.7074 | likely_pathogenic | 0.6572 | pathogenic | -1.753 | Destabilizing | 0.789 | D | 0.869 | deleterious | None | None | None | None | N |
| I/R | 0.6513 | likely_pathogenic | 0.6031 | pathogenic | -1.269 | Destabilizing | 0.481 | N | 0.868 | deleterious | N | 0.489553897 | None | None | N |
| I/S | 0.537 | ambiguous | 0.5022 | ambiguous | -2.611 | Highly Destabilizing | 0.378 | N | 0.76 | deleterious | None | None | None | None | N |
| I/T | 0.389 | ambiguous | 0.3454 | ambiguous | -2.261 | Highly Destabilizing | 0.061 | N | 0.735 | deleterious | N | 0.48803296 | None | None | N |
| I/V | 0.0569 | likely_benign | 0.0565 | benign | -1.211 | Destabilizing | None | N | 0.173 | neutral | N | 0.493762076 | None | None | N |
| I/W | 0.8657 | likely_pathogenic | 0.8656 | pathogenic | -1.363 | Destabilizing | 0.934 | D | 0.852 | deleterious | None | None | None | None | N |
| I/Y | 0.6655 | likely_pathogenic | 0.6283 | pathogenic | -1.112 | Destabilizing | 0.552 | D | 0.797 | deleterious | 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.