Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33316 | 100171;100172;100173 | chr2:178537163;178537162;178537161 | chr2:179401890;179401889;179401888 |
| N2AB | 31675 | 95248;95249;95250 | chr2:178537163;178537162;178537161 | chr2:179401890;179401889;179401888 |
| N2A | 30748 | 92467;92468;92469 | chr2:178537163;178537162;178537161 | chr2:179401890;179401889;179401888 |
| N2B | 24251 | 72976;72977;72978 | chr2:178537163;178537162;178537161 | chr2:179401890;179401889;179401888 |
| Novex-1 | 24376 | 73351;73352;73353 | chr2:178537163;178537162;178537161 | chr2:179401890;179401889;179401888 |
| Novex-2 | 24443 | 73552;73553;73554 | chr2:178537163;178537162;178537161 | chr2:179401890;179401889;179401888 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs374295768  |
-0.239 | 0.004 | N | 0.094 | 0.042 | None | gnomAD-2.1.1 | 2.50374E-04 | None | None | None | None | I | None | 4.14E-05 | 1.13417E-04 | None | 2.8079E-03 | 5.14E-05 | None | 9.49077E-04 | None | 0 | 3.13E-05 | 2.82087E-04 |
| A/T | rs374295768 |
-0.239 | 0.004 | N | 0.094 | 0.042 | None | gnomAD-3.1.2 | 1.44604E-04 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 2.59217E-03 | 0 | None | 0 | 0 | 5.88E-05 | 1.45168E-03 | 0 |
| A/T | rs374295768 |
-0.239 | 0.004 | N | 0.094 | 0.042 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| A/T | rs374295768 |
-0.239 | 0.004 | N | 0.094 | 0.042 | None | gnomAD-4.0.0 | 1.3634E-04 | None | None | None | None | I | None | 3.99925E-05 | 6.66889E-05 | None | 2.3314E-03 | 2.22946E-05 | None | 0 | 0 | 3.30589E-05 | 1.03238E-03 | 1.60092E-04 |
| A/V | rs1406589986 |
-0.051 | 0.001 | N | 0.097 | 0.042 | 0.180583059064 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5139 | ambiguous | 0.531 | ambiguous | -0.595 | Destabilizing | 0.667 | D | 0.275 | neutral | None | None | None | None | I |
| A/D | 0.1836 | likely_benign | 0.1909 | benign | -0.581 | Destabilizing | 0.055 | N | 0.319 | neutral | None | None | None | None | I |
| A/E | 0.0901 | likely_benign | 0.0965 | benign | -0.753 | Destabilizing | None | N | 0.121 | neutral | N | 0.400038265 | None | None | I |
| A/F | 0.3673 | ambiguous | 0.3647 | ambiguous | -0.931 | Destabilizing | 0.667 | D | 0.405 | neutral | None | None | None | None | I |
| A/G | 0.1683 | likely_benign | 0.1649 | benign | -0.151 | Destabilizing | None | N | 0.081 | neutral | N | 0.479059196 | None | None | I |
| A/H | 0.3843 | ambiguous | 0.387 | ambiguous | -0.267 | Destabilizing | 0.667 | D | 0.341 | neutral | None | None | None | None | I |
| A/I | 0.1513 | likely_benign | 0.1677 | benign | -0.3 | Destabilizing | 0.004 | N | 0.163 | neutral | None | None | None | None | I |
| A/K | 0.1753 | likely_benign | 0.1841 | benign | -0.45 | Destabilizing | 0.002 | N | 0.121 | neutral | None | None | None | None | I |
| A/L | 0.1202 | likely_benign | 0.1298 | benign | -0.3 | Destabilizing | 0.055 | N | 0.309 | neutral | None | None | None | None | I |
| A/M | 0.162 | likely_benign | 0.1746 | benign | -0.272 | Destabilizing | 0.667 | D | 0.295 | neutral | None | None | None | None | I |
| A/N | 0.1821 | likely_benign | 0.2005 | benign | -0.084 | Destabilizing | 0.22 | N | 0.378 | neutral | None | None | None | None | I |
| A/P | 0.2913 | likely_benign | 0.266 | benign | -0.216 | Destabilizing | 0.523 | D | 0.39 | neutral | N | 0.452352597 | None | None | I |
| A/Q | 0.1592 | likely_benign | 0.1646 | benign | -0.415 | Destabilizing | 0.124 | N | 0.393 | neutral | None | None | None | None | I |
| A/R | 0.2089 | likely_benign | 0.2005 | benign | 0.022 | Stabilizing | 0.124 | N | 0.349 | neutral | None | None | None | None | I |
| A/S | 0.1036 | likely_benign | 0.1006 | benign | -0.221 | Destabilizing | 0.1 | N | 0.187 | neutral | N | 0.433766836 | None | None | I |
| A/T | 0.0777 | likely_benign | 0.0806 | benign | -0.326 | Destabilizing | 0.004 | N | 0.094 | neutral | N | 0.434940272 | None | None | I |
| A/V | 0.0924 | likely_benign | 0.0959 | benign | -0.216 | Destabilizing | 0.001 | N | 0.097 | neutral | N | 0.455990335 | None | None | I |
| A/W | 0.7193 | likely_pathogenic | 0.7045 | pathogenic | -1.06 | Destabilizing | 0.958 | D | 0.313 | neutral | None | None | None | None | I |
| A/Y | 0.4817 | ambiguous | 0.4845 | ambiguous | -0.696 | Destabilizing | 0.667 | D | 0.395 | neutral | None | None | None | None | I |
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.