Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13884 | 41875;41876;41877 | chr2:178635674;178635673;178635672 | chr2:179500401;179500400;179500399 |
| N2AB | 12243 | 36952;36953;36954 | chr2:178635674;178635673;178635672 | chr2:179500401;179500400;179500399 |
| N2A | 11316 | 34171;34172;34173 | chr2:178635674;178635673;178635672 | chr2:179500401;179500400;179500399 |
| N2B | 4819 | 14680;14681;14682 | chr2:178635674;178635673;178635672 | chr2:179500401;179500400;179500399 |
| Novex-1 | 4944 | 15055;15056;15057 | chr2:178635674;178635673;178635672 | chr2:179500401;179500400;179500399 |
| Novex-2 | 5011 | 15256;15257;15258 | chr2:178635674;178635673;178635672 | chr2:179500401;179500400;179500399 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/Q | rs1361052408  |
0.195 | 0.988 | N | 0.517 | 0.204 | 0.177238962908 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| H/Q | rs1361052408 |
0.195 | 0.988 | N | 0.517 | 0.204 | 0.177238962908 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| H/Q | rs1361052408 |
0.195 | 0.988 | N | 0.517 | 0.204 | 0.177238962908 | gnomAD-4.0.0 | 2.49721E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.40783E-06 | 0 | 0 |
| H/R | rs1432673437 |
-0.02 | 0.92 | N | 0.509 | 0.268 | 0.17948927462 | gnomAD-2.1.1 | 4.34E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.54E-05 | None | 0 | 0 | 0 |
| H/R | rs1432673437 |
-0.02 | 0.92 | N | 0.509 | 0.268 | 0.17948927462 | gnomAD-4.0.0 | 6.89733E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.23444E-06 | 1.18649E-05 | 1.66722E-05 |
| H/Y | None | None | 0.993 | N | 0.515 | 0.416 | 0.198526703765 | gnomAD-4.0.0 | 1.62177E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.91476E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.8978 | likely_pathogenic | 0.9006 | pathogenic | 0.321 | Stabilizing | 0.968 | D | 0.468 | neutral | None | None | None | None | N |
| H/C | 0.8142 | likely_pathogenic | 0.8067 | pathogenic | 0.493 | Stabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| H/D | 0.8714 | likely_pathogenic | 0.8701 | pathogenic | -0.266 | Destabilizing | 0.994 | D | 0.508 | neutral | N | 0.49577735 | None | None | N |
| H/E | 0.8932 | likely_pathogenic | 0.8993 | pathogenic | -0.265 | Destabilizing | 0.968 | D | 0.48 | neutral | None | None | None | None | N |
| H/F | 0.7157 | likely_pathogenic | 0.707 | pathogenic | 0.831 | Stabilizing | 0.998 | D | 0.5 | neutral | None | None | None | None | N |
| H/G | 0.9519 | likely_pathogenic | 0.9581 | pathogenic | 0.102 | Stabilizing | 0.984 | D | 0.489 | neutral | None | None | None | None | N |
| H/I | 0.8706 | likely_pathogenic | 0.8703 | pathogenic | 0.86 | Stabilizing | 0.998 | D | 0.694 | prob.delet. | None | None | None | None | N |
| H/K | 0.8821 | likely_pathogenic | 0.892 | pathogenic | 0.161 | Stabilizing | 0.29 | N | 0.402 | neutral | None | None | None | None | N |
| H/L | 0.628 | likely_pathogenic | 0.6143 | pathogenic | 0.86 | Stabilizing | 0.994 | D | 0.555 | neutral | N | 0.489655811 | None | None | N |
| H/M | 0.8876 | likely_pathogenic | 0.9022 | pathogenic | 0.572 | Stabilizing | 1.0 | D | 0.616 | neutral | None | None | None | None | N |
| H/N | 0.6009 | likely_pathogenic | 0.597 | pathogenic | 0.049 | Stabilizing | 0.979 | D | 0.501 | neutral | N | 0.457088776 | None | None | N |
| H/P | 0.8538 | likely_pathogenic | 0.8432 | pathogenic | 0.704 | Stabilizing | 0.998 | D | 0.639 | neutral | N | 0.495992709 | None | None | N |
| H/Q | 0.8367 | likely_pathogenic | 0.8378 | pathogenic | 0.114 | Stabilizing | 0.988 | D | 0.517 | neutral | N | 0.493168374 | None | None | N |
| H/R | 0.7552 | likely_pathogenic | 0.7541 | pathogenic | -0.312 | Destabilizing | 0.92 | D | 0.509 | neutral | N | 0.493168374 | None | None | N |
| H/S | 0.8624 | likely_pathogenic | 0.8716 | pathogenic | 0.189 | Stabilizing | 0.968 | D | 0.549 | neutral | None | None | None | None | N |
| H/T | 0.8814 | likely_pathogenic | 0.8975 | pathogenic | 0.28 | Stabilizing | 0.995 | D | 0.469 | neutral | None | None | None | None | N |
| H/V | 0.8421 | likely_pathogenic | 0.8473 | pathogenic | 0.704 | Stabilizing | 0.995 | D | 0.645 | neutral | None | None | None | None | N |
| H/W | 0.7921 | likely_pathogenic | 0.7852 | pathogenic | 0.726 | Stabilizing | 1.0 | D | 0.684 | prob.delet. | None | None | None | None | N |
| H/Y | 0.4676 | ambiguous | 0.4414 | ambiguous | 0.989 | Stabilizing | 0.993 | D | 0.515 | neutral | N | 0.493168374 | 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.