Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21562 | 64909;64910;64911 | chr2:178584957;178584956;178584955 | chr2:179449684;179449683;179449682 |
| N2AB | 19921 | 59986;59987;59988 | chr2:178584957;178584956;178584955 | chr2:179449684;179449683;179449682 |
| N2A | 18994 | 57205;57206;57207 | chr2:178584957;178584956;178584955 | chr2:179449684;179449683;179449682 |
| N2B | 12497 | 37714;37715;37716 | chr2:178584957;178584956;178584955 | chr2:179449684;179449683;179449682 |
| Novex-1 | 12622 | 38089;38090;38091 | chr2:178584957;178584956;178584955 | chr2:179449684;179449683;179449682 |
| Novex-2 | 12689 | 38290;38291;38292 | chr2:178584957;178584956;178584955 | chr2:179449684;179449683;179449682 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 1.0 | N | 0.711 | 0.436 | 0.690156929516 | gnomAD-4.0.0 | 6.84508E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16058E-05 | 0 |
| P/R | rs1213776805  |
None | 1.0 | N | 0.719 | 0.457 | 0.51759925163 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/R | rs1213776805 |
None | 1.0 | N | 0.719 | 0.457 | 0.51759925163 | gnomAD-4.0.0 | 6.57497E-06 | None | None | None | None | I | None | 2.41324E-05 | 0 | None | 0 | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1373 | likely_benign | 0.116 | benign | -1.702 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | N | 0.504797428 | None | None | I |
| P/C | 0.6358 | likely_pathogenic | 0.5744 | pathogenic | -1.271 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| P/D | 0.8906 | likely_pathogenic | 0.8489 | pathogenic | -2.464 | Highly Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | I |
| P/E | 0.5927 | likely_pathogenic | 0.5119 | ambiguous | -2.453 | Highly Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| P/F | 0.6836 | likely_pathogenic | 0.6185 | pathogenic | -1.362 | Destabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | I |
| P/G | 0.7177 | likely_pathogenic | 0.6471 | pathogenic | -2.021 | Highly Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| P/H | 0.4865 | ambiguous | 0.4313 | ambiguous | -1.62 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | N | 0.510984336 | None | None | I |
| P/I | 0.3035 | likely_benign | 0.2613 | benign | -0.902 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | I |
| P/K | 0.4394 | ambiguous | 0.4007 | ambiguous | -1.465 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | I |
| P/L | 0.2028 | likely_benign | 0.1829 | benign | -0.902 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | N | 0.48534521 | None | None | I |
| P/M | 0.4006 | ambiguous | 0.3508 | ambiguous | -0.707 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | I |
| P/N | 0.7493 | likely_pathogenic | 0.6684 | pathogenic | -1.387 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| P/Q | 0.3277 | likely_benign | 0.2818 | benign | -1.596 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | I |
| P/R | 0.3612 | ambiguous | 0.328 | benign | -0.915 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | N | 0.481421644 | None | None | I |
| P/S | 0.3476 | ambiguous | 0.2847 | benign | -1.784 | Destabilizing | 1.0 | D | 0.747 | deleterious | N | 0.480407685 | None | None | I |
| P/T | 0.2797 | likely_benign | 0.2351 | benign | -1.68 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.502968939 | None | None | I |
| P/V | 0.2542 | likely_benign | 0.217 | benign | -1.138 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | I |
| P/W | 0.8976 | likely_pathogenic | 0.8857 | pathogenic | -1.636 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | I |
| P/Y | 0.732 | likely_pathogenic | 0.6809 | pathogenic | -1.348 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
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.