Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5220 | 15883;15884;15885 | chr2:178733731;178733730;178733729 | chr2:179598458;179598457;179598456 |
| N2AB | 4903 | 14932;14933;14934 | chr2:178733731;178733730;178733729 | chr2:179598458;179598457;179598456 |
| N2A | 3976 | 12151;12152;12153 | chr2:178733731;178733730;178733729 | chr2:179598458;179598457;179598456 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | rs1235055882  |
0.412 | 0.062 | N | 0.356 | 0.136 | 0.143124449307 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| N/D | rs1235055882 |
0.412 | 0.062 | N | 0.356 | 0.136 | 0.143124449307 | gnomAD-4.0.0 | 4.77345E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.57461E-06 | 0 | 0 |
| N/S | rs565670799 |
0.084 | None | N | 0.193 | 0.11 | 0.0297737177859 | gnomAD-2.1.1 | 3.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.61438E-04 | None | 0 | 7.8E-06 | 0 |
| N/S | rs565670799 |
0.084 | None | N | 0.193 | 0.11 | 0.0297737177859 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 0 | 1.30993E-04 | 0 | 0 | 1.92604E-04 | None | 0 | 0 | 2.94E-05 | 4.14079E-04 | 0 |
| N/S | rs565670799 |
0.084 | None | N | 0.193 | 0.11 | 0.0297737177859 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| N/S | rs565670799 |
0.084 | None | N | 0.193 | 0.11 | 0.0297737177859 | gnomAD-4.0.0 | 3.1601E-05 | None | None | None | None | N | None | 0 | 3.33278E-05 | None | 0 | 2.22846E-05 | None | 0 | 0 | 9.32368E-06 | 3.95248E-04 | 1.60061E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.1268 | likely_benign | 0.1634 | benign | -0.105 | Destabilizing | 0.081 | N | 0.363 | neutral | None | None | None | None | N |
| N/C | 0.1964 | likely_benign | 0.247 | benign | -0.104 | Destabilizing | 0.824 | D | 0.386 | neutral | None | None | None | None | N |
| N/D | 0.0777 | likely_benign | 0.086 | benign | 0.03 | Stabilizing | 0.062 | N | 0.356 | neutral | N | 0.422627239 | None | None | N |
| N/E | 0.1905 | likely_benign | 0.216 | benign | -0.037 | Destabilizing | 0.081 | N | 0.335 | neutral | None | None | None | None | N |
| N/F | 0.4062 | ambiguous | 0.4932 | ambiguous | -0.792 | Destabilizing | 0.555 | D | 0.346 | neutral | None | None | None | None | N |
| N/G | 0.1221 | likely_benign | 0.1551 | benign | -0.154 | Destabilizing | 0.035 | N | 0.345 | neutral | None | None | None | None | N |
| N/H | 0.0833 | likely_benign | 0.0911 | benign | -0.141 | Destabilizing | 0.001 | N | 0.304 | neutral | N | 0.494247157 | None | None | N |
| N/I | 0.2746 | likely_benign | 0.3291 | benign | -0.075 | Destabilizing | 0.317 | N | 0.35 | neutral | D | 0.56993012 | None | None | N |
| N/K | 0.1568 | likely_benign | 0.1638 | benign | 0.011 | Stabilizing | None | N | 0.239 | neutral | N | 0.438909044 | None | None | N |
| N/L | 0.2012 | likely_benign | 0.2305 | benign | -0.075 | Destabilizing | 0.149 | N | 0.376 | neutral | None | None | None | None | N |
| N/M | 0.2784 | likely_benign | 0.3231 | benign | -0.106 | Destabilizing | 0.935 | D | 0.336 | neutral | None | None | None | None | N |
| N/P | 0.4227 | ambiguous | 0.5708 | pathogenic | -0.066 | Destabilizing | 0.38 | N | 0.343 | neutral | None | None | None | None | N |
| N/Q | 0.1868 | likely_benign | 0.2078 | benign | -0.4 | Destabilizing | 0.38 | N | 0.299 | neutral | None | None | None | None | N |
| N/R | 0.1655 | likely_benign | 0.1825 | benign | 0.077 | Stabilizing | 0.081 | N | 0.329 | neutral | None | None | None | None | N |
| N/S | 0.062 | likely_benign | 0.0566 | benign | -0.208 | Destabilizing | None | N | 0.193 | neutral | N | 0.446725833 | None | None | N |
| N/T | 0.1205 | likely_benign | 0.1483 | benign | -0.174 | Destabilizing | 0.062 | N | 0.337 | neutral | N | 0.461829693 | None | None | N |
| N/V | 0.243 | likely_benign | 0.2978 | benign | -0.066 | Destabilizing | 0.38 | N | 0.361 | neutral | None | None | None | None | N |
| N/W | 0.5596 | ambiguous | 0.6543 | pathogenic | -0.978 | Destabilizing | 0.935 | D | 0.494 | neutral | None | None | None | None | N |
| N/Y | 0.1404 | likely_benign | 0.1577 | benign | -0.638 | Destabilizing | 0.317 | N | 0.335 | neutral | D | 0.56993012 | 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.