Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34993 | 105202;105203;105204 | chr2:178531638;178531637;178531636 | chr2:179396365;179396364;179396363 |
| N2AB | 33352 | 100279;100280;100281 | chr2:178531638;178531637;178531636 | chr2:179396365;179396364;179396363 |
| N2A | 32425 | 97498;97499;97500 | chr2:178531638;178531637;178531636 | chr2:179396365;179396364;179396363 |
| N2B | 25928 | 78007;78008;78009 | chr2:178531638;178531637;178531636 | chr2:179396365;179396364;179396363 |
| Novex-1 | 26053 | 78382;78383;78384 | chr2:178531638;178531637;178531636 | chr2:179396365;179396364;179396363 |
| Novex-2 | 26120 | 78583;78584;78585 | chr2:178531638;178531637;178531636 | chr2:179396365;179396364;179396363 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/M | rs368945564  |
0.041 | 0.004 | N | 0.197 | 0.165 | None | gnomAD-2.1.1 | 5.22E-05 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 1.63409E-04 | None | 0 | 6.2E-05 | 0 |
| T/M | rs368945564 |
0.041 | 0.004 | N | 0.197 | 0.165 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.9253E-04 | None | 0 | 0 | 8.82E-05 | 0 | 0 |
| T/M | rs368945564 |
0.041 | 0.004 | N | 0.197 | 0.165 | None | gnomAD-4.0.0 | 9.72742E-05 | None | None | None | None | N | None | 2.66496E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.19504E-04 | 1.20765E-04 | 4.80123E-05 |
| T/R | None | None | 0.541 | N | 0.274 | 0.176 | 0.211220785272 | gnomAD-4.0.0 | 6.84147E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99399E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1182 | likely_benign | 0.149 | benign | -0.319 | Destabilizing | 0.027 | N | 0.219 | neutral | N | 0.463583603 | None | None | N |
| T/C | 0.5981 | likely_pathogenic | 0.6459 | pathogenic | -0.157 | Destabilizing | 0.935 | D | 0.233 | neutral | None | None | None | None | N |
| T/D | 0.4863 | ambiguous | 0.6677 | pathogenic | 0.172 | Stabilizing | 0.555 | D | 0.277 | neutral | None | None | None | None | N |
| T/E | 0.3313 | likely_benign | 0.5023 | ambiguous | 0.079 | Stabilizing | 0.262 | N | 0.278 | neutral | None | None | None | None | N |
| T/F | 0.2892 | likely_benign | 0.4275 | ambiguous | -0.932 | Destabilizing | 0.38 | N | 0.324 | neutral | None | None | None | None | N |
| T/G | 0.355 | ambiguous | 0.4381 | ambiguous | -0.407 | Destabilizing | 0.149 | N | 0.339 | neutral | None | None | None | None | N |
| T/H | 0.2864 | likely_benign | 0.3832 | ambiguous | -0.755 | Destabilizing | 0.935 | D | 0.286 | neutral | None | None | None | None | N |
| T/I | 0.159 | likely_benign | 0.2508 | benign | -0.21 | Destabilizing | 0.035 | N | 0.258 | neutral | None | None | None | None | N |
| T/K | 0.1836 | likely_benign | 0.317 | benign | -0.217 | Destabilizing | 0.251 | N | 0.303 | neutral | N | 0.475491321 | None | None | N |
| T/L | 0.09 | likely_benign | 0.1223 | benign | -0.21 | Destabilizing | None | N | 0.204 | neutral | None | None | None | None | N |
| T/M | 0.0619 | likely_benign | 0.07 | benign | 0.058 | Stabilizing | 0.004 | N | 0.197 | neutral | N | 0.495157304 | None | None | N |
| T/N | 0.1782 | likely_benign | 0.2256 | benign | 0.022 | Stabilizing | 0.555 | D | 0.228 | neutral | None | None | None | None | N |
| T/P | 0.407 | ambiguous | 0.5535 | ambiguous | -0.221 | Destabilizing | 0.741 | D | 0.273 | neutral | N | 0.47495539 | None | None | N |
| T/Q | 0.1934 | likely_benign | 0.2668 | benign | -0.244 | Destabilizing | 0.38 | N | 0.272 | neutral | None | None | None | None | N |
| T/R | 0.146 | likely_benign | 0.2697 | benign | 0.034 | Stabilizing | 0.541 | D | 0.274 | neutral | N | 0.469874857 | None | None | N |
| T/S | 0.1489 | likely_benign | 0.1813 | benign | -0.177 | Destabilizing | 0.117 | N | 0.201 | neutral | N | 0.467026553 | None | None | N |
| T/V | 0.1141 | likely_benign | 0.1564 | benign | -0.221 | Destabilizing | None | N | 0.155 | neutral | None | None | None | None | N |
| T/W | 0.6305 | likely_pathogenic | 0.7883 | pathogenic | -0.945 | Destabilizing | 0.935 | D | 0.316 | neutral | None | None | None | None | N |
| T/Y | 0.3844 | ambiguous | 0.5119 | ambiguous | -0.646 | Destabilizing | 0.555 | D | 0.311 | 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.