Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30637 | 92134;92135;92136 | chr2:178549813;178549812;178549811 | chr2:179414540;179414539;179414538 |
| N2AB | 28996 | 87211;87212;87213 | chr2:178549813;178549812;178549811 | chr2:179414540;179414539;179414538 |
| N2A | 28069 | 84430;84431;84432 | chr2:178549813;178549812;178549811 | chr2:179414540;179414539;179414538 |
| N2B | 21572 | 64939;64940;64941 | chr2:178549813;178549812;178549811 | chr2:179414540;179414539;179414538 |
| Novex-1 | 21697 | 65314;65315;65316 | chr2:178549813;178549812;178549811 | chr2:179414540;179414539;179414538 |
| Novex-2 | 21764 | 65515;65516;65517 | chr2:178549813;178549812;178549811 | chr2:179414540;179414539;179414538 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/K | rs1698605663  |
None | 0.302 | N | 0.61 | 0.377 | 0.524013290319 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/K | rs1698605663 |
None | 0.302 | N | 0.61 | 0.377 | 0.524013290319 | gnomAD-4.0.0 | 6.57125E-06 | None | None | None | None | N | None | 0 | 6.54793E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | None | None | 0.159 | N | 0.557 | 0.22 | 0.538698623518 | gnomAD-4.0.0 | 6.87869E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.04179E-07 | 0 | 0 |
| M/V | rs751394805 |
0.392 | None | N | 0.169 | 0.154 | 0.273503213844 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| M/V | rs751394805 |
0.392 | None | N | 0.169 | 0.154 | 0.273503213844 | gnomAD-4.0.0 | 4.81795E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.3319E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5762 | likely_pathogenic | 0.6181 | pathogenic | -2.009 | Highly Destabilizing | 0.001 | N | 0.364 | neutral | None | None | None | None | N |
| M/C | 0.7862 | likely_pathogenic | 0.7668 | pathogenic | -2.528 | Highly Destabilizing | 0.001 | N | 0.441 | neutral | None | None | None | None | N |
| M/D | 0.9973 | likely_pathogenic | 0.9985 | pathogenic | -2.138 | Highly Destabilizing | 0.738 | D | 0.709 | prob.delet. | None | None | None | None | N |
| M/E | 0.9776 | likely_pathogenic | 0.9877 | pathogenic | -1.864 | Destabilizing | 0.365 | N | 0.643 | neutral | None | None | None | None | N |
| M/F | 0.7013 | likely_pathogenic | 0.7693 | pathogenic | -0.603 | Destabilizing | 0.582 | D | 0.569 | neutral | None | None | None | None | N |
| M/G | 0.9106 | likely_pathogenic | 0.9398 | pathogenic | -2.523 | Highly Destabilizing | 0.111 | N | 0.64 | neutral | None | None | None | None | N |
| M/H | 0.9822 | likely_pathogenic | 0.9894 | pathogenic | -2.406 | Highly Destabilizing | 0.968 | D | 0.726 | prob.delet. | None | None | None | None | N |
| M/I | 0.38 | ambiguous | 0.4578 | ambiguous | -0.515 | Destabilizing | 0.039 | N | 0.405 | neutral | N | 0.409166675 | None | None | N |
| M/K | 0.9302 | likely_pathogenic | 0.9665 | pathogenic | -1.224 | Destabilizing | 0.302 | N | 0.61 | neutral | N | 0.4663879 | None | None | N |
| M/L | 0.1734 | likely_benign | 0.2287 | benign | -0.515 | Destabilizing | None | N | 0.16 | neutral | N | 0.408841388 | None | None | N |
| M/N | 0.9668 | likely_pathogenic | 0.9784 | pathogenic | -1.782 | Destabilizing | 0.738 | D | 0.733 | prob.delet. | None | None | None | None | N |
| M/P | 0.9959 | likely_pathogenic | 0.9983 | pathogenic | -0.997 | Destabilizing | 0.738 | D | 0.697 | prob.neutral | None | None | None | None | N |
| M/Q | 0.897 | likely_pathogenic | 0.9285 | pathogenic | -1.349 | Destabilizing | 0.738 | D | 0.655 | neutral | None | None | None | None | N |
| M/R | 0.9284 | likely_pathogenic | 0.9667 | pathogenic | -1.604 | Destabilizing | 0.68 | D | 0.701 | prob.neutral | N | 0.4663879 | None | None | N |
| M/S | 0.8782 | likely_pathogenic | 0.9059 | pathogenic | -2.274 | Highly Destabilizing | 0.111 | N | 0.557 | neutral | None | None | None | None | N |
| M/T | 0.6799 | likely_pathogenic | 0.7645 | pathogenic | -1.853 | Destabilizing | 0.159 | N | 0.557 | neutral | N | 0.511280684 | None | None | N |
| M/V | 0.1268 | likely_benign | 0.1425 | benign | -0.997 | Destabilizing | None | N | 0.169 | neutral | N | 0.345096554 | None | None | N |
| M/W | 0.9753 | likely_pathogenic | 0.9895 | pathogenic | -0.985 | Destabilizing | 0.968 | D | 0.73 | prob.delet. | None | None | None | None | N |
| M/Y | 0.9397 | likely_pathogenic | 0.964 | pathogenic | -0.927 | Destabilizing | 0.896 | D | 0.739 | prob.delet. | 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.