Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15981 | 48166;48167;48168 | chr2:178616948;178616947;178616946 | chr2:179481675;179481674;179481673 |
| N2AB | 14340 | 43243;43244;43245 | chr2:178616948;178616947;178616946 | chr2:179481675;179481674;179481673 |
| N2A | 13413 | 40462;40463;40464 | chr2:178616948;178616947;178616946 | chr2:179481675;179481674;179481673 |
| N2B | 6916 | 20971;20972;20973 | chr2:178616948;178616947;178616946 | chr2:179481675;179481674;179481673 |
| Novex-1 | 7041 | 21346;21347;21348 | chr2:178616948;178616947;178616946 | chr2:179481675;179481674;179481673 |
| Novex-2 | 7108 | 21547;21548;21549 | chr2:178616948;178616947;178616946 | chr2:179481675;179481674;179481673 |
| 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 | rs150364979  |
-0.074 | 0.702 | N | 0.457 | 0.123 | None | gnomAD-2.1.1 | 3.94E-05 | None | None | None | None | N | None | 1.24121E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.29E-05 | 0 |
| T/M | rs150364979 |
-0.074 | 0.702 | N | 0.457 | 0.123 | None | gnomAD-3.1.2 | 4.61E-05 | None | None | None | None | N | None | 7.25E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.89E-05 | 0 | 0 |
| T/M | rs150364979 |
-0.074 | 0.702 | N | 0.457 | 0.123 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| T/M | rs150364979 |
-0.074 | 0.702 | N | 0.457 | 0.123 | None | gnomAD-4.0.0 | 3.53451E-05 | None | None | None | None | N | None | 8.0094E-05 | 0 | None | 0 | 2.23524E-05 | None | 0 | 0 | 4.1557E-05 | 0 | 1.60205E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1031 | likely_benign | 0.1049 | benign | -0.583 | Destabilizing | 0.005 | N | 0.305 | neutral | N | 0.461972279 | None | None | N |
| T/C | 0.3708 | ambiguous | 0.3515 | ambiguous | -0.499 | Destabilizing | 0.628 | D | 0.45 | neutral | None | None | None | None | N |
| T/D | 0.4688 | ambiguous | 0.4388 | ambiguous | 0.059 | Stabilizing | 0.072 | N | 0.471 | neutral | None | None | None | None | N |
| T/E | 0.233 | likely_benign | 0.2057 | benign | 0.142 | Stabilizing | 0.016 | N | 0.414 | neutral | None | None | None | None | N |
| T/F | 0.371 | ambiguous | 0.3466 | ambiguous | -0.556 | Destabilizing | 0.356 | N | 0.483 | neutral | None | None | None | None | N |
| T/G | 0.3507 | ambiguous | 0.3288 | benign | -0.896 | Destabilizing | 0.031 | N | 0.437 | neutral | None | None | None | None | N |
| T/H | 0.1705 | likely_benign | 0.1445 | benign | -1.003 | Destabilizing | 0.356 | N | 0.453 | neutral | None | None | None | None | N |
| T/I | 0.1941 | likely_benign | 0.1913 | benign | 0.173 | Stabilizing | 0.038 | N | 0.475 | neutral | None | None | None | None | N |
| T/K | 0.0774 | likely_benign | 0.0604 | benign | -0.391 | Destabilizing | None | N | 0.293 | neutral | N | 0.386099062 | None | None | N |
| T/L | 0.1376 | likely_benign | 0.1377 | benign | 0.173 | Stabilizing | 0.016 | N | 0.388 | neutral | None | None | None | None | N |
| T/M | 0.1271 | likely_benign | 0.1191 | benign | 0.016 | Stabilizing | 0.702 | D | 0.457 | neutral | N | 0.461536274 | None | None | N |
| T/N | 0.1418 | likely_benign | 0.1328 | benign | -0.656 | Destabilizing | 0.072 | N | 0.413 | neutral | None | None | None | None | N |
| T/P | 0.3616 | ambiguous | 0.4266 | ambiguous | -0.045 | Destabilizing | 0.106 | N | 0.465 | neutral | N | 0.461760832 | None | None | N |
| T/Q | 0.139 | likely_benign | 0.1155 | benign | -0.568 | Destabilizing | 0.038 | N | 0.464 | neutral | None | None | None | None | N |
| T/R | 0.0794 | likely_benign | 0.0672 | benign | -0.378 | Destabilizing | None | N | 0.259 | neutral | N | 0.412555857 | None | None | N |
| T/S | 0.1432 | likely_benign | 0.1374 | benign | -0.955 | Destabilizing | 0.001 | N | 0.243 | neutral | N | 0.413489591 | None | None | N |
| T/V | 0.1457 | likely_benign | 0.1545 | benign | -0.045 | Destabilizing | None | N | 0.229 | neutral | None | None | None | None | N |
| T/W | 0.6282 | likely_pathogenic | 0.5859 | pathogenic | -0.628 | Destabilizing | 0.864 | D | 0.471 | neutral | None | None | None | None | N |
| T/Y | 0.2843 | likely_benign | 0.2669 | benign | -0.29 | Destabilizing | 0.356 | N | 0.481 | 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.