Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14925 | 44998;44999;45000 | chr2:178624507;178624506;178624505 | chr2:179489234;179489233;179489232 |
| N2AB | 13284 | 40075;40076;40077 | chr2:178624507;178624506;178624505 | chr2:179489234;179489233;179489232 |
| N2A | 12357 | 37294;37295;37296 | chr2:178624507;178624506;178624505 | chr2:179489234;179489233;179489232 |
| N2B | 5860 | 17803;17804;17805 | chr2:178624507;178624506;178624505 | chr2:179489234;179489233;179489232 |
| Novex-1 | 5985 | 18178;18179;18180 | chr2:178624507;178624506;178624505 | chr2:179489234;179489233;179489232 |
| Novex-2 | 6052 | 18379;18380;18381 | chr2:178624507;178624506;178624505 | chr2:179489234;179489233;179489232 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs775846804  |
-1.352 | 0.217 | N | 0.414 | 0.327 | 0.270447802918 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.28863E-04 | None | 0 | 0 | 0 |
| D/G | rs775846804 |
-1.352 | 0.217 | N | 0.414 | 0.327 | 0.270447802918 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.13907E-04 | 0 |
| D/G | rs775846804 |
-1.352 | 0.217 | N | 0.414 | 0.327 | 0.270447802918 | gnomAD-4.0.0 | 8.68114E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.53765E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3023 | likely_benign | 0.433 | ambiguous | -0.681 | Destabilizing | 0.543 | D | 0.545 | neutral | N | 0.50727061 | None | None | N |
| D/C | 0.8474 | likely_pathogenic | 0.9111 | pathogenic | -0.345 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | N |
| D/E | 0.3795 | ambiguous | 0.5116 | ambiguous | -0.715 | Destabilizing | 0.994 | D | 0.551 | neutral | N | 0.4177174 | None | None | N |
| D/F | 0.7516 | likely_pathogenic | 0.8495 | pathogenic | -0.342 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| D/G | 0.5171 | ambiguous | 0.6603 | pathogenic | -1.097 | Destabilizing | 0.217 | N | 0.414 | neutral | N | 0.510231113 | None | None | N |
| D/H | 0.4861 | ambiguous | 0.6523 | pathogenic | -0.704 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | N | 0.504685472 | None | None | N |
| D/I | 0.4953 | ambiguous | 0.6506 | pathogenic | 0.446 | Stabilizing | 0.999 | D | 0.807 | deleterious | None | None | None | None | N |
| D/K | 0.6517 | likely_pathogenic | 0.8107 | pathogenic | -0.774 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| D/L | 0.5803 | likely_pathogenic | 0.7077 | pathogenic | 0.446 | Stabilizing | 0.998 | D | 0.783 | deleterious | None | None | None | None | N |
| D/M | 0.8068 | likely_pathogenic | 0.8803 | pathogenic | 1.027 | Stabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| D/N | 0.1785 | likely_benign | 0.2516 | benign | -1.141 | Destabilizing | 0.998 | D | 0.633 | neutral | N | 0.508815174 | None | None | N |
| D/P | 0.9744 | likely_pathogenic | 0.9875 | pathogenic | 0.095 | Stabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| D/Q | 0.627 | likely_pathogenic | 0.7662 | pathogenic | -0.9 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | N |
| D/R | 0.6454 | likely_pathogenic | 0.8052 | pathogenic | -0.716 | Destabilizing | 0.999 | D | 0.779 | deleterious | None | None | None | None | N |
| D/S | 0.2405 | likely_benign | 0.3403 | ambiguous | -1.608 | Destabilizing | 0.983 | D | 0.577 | neutral | None | None | None | None | N |
| D/T | 0.4549 | ambiguous | 0.6288 | pathogenic | -1.244 | Destabilizing | 0.998 | D | 0.693 | prob.neutral | None | None | None | None | N |
| D/V | 0.3176 | likely_benign | 0.4498 | ambiguous | 0.095 | Stabilizing | 0.997 | D | 0.765 | deleterious | N | 0.461816298 | None | None | N |
| D/W | 0.9452 | likely_pathogenic | 0.9712 | pathogenic | -0.308 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| D/Y | 0.3611 | ambiguous | 0.4987 | ambiguous | -0.123 | Destabilizing | 1.0 | D | 0.792 | deleterious | N | 0.507653325 | 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.