Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23389 | 70390;70391;70392 | chr2:178575967;178575966;178575965 | chr2:179440694;179440693;179440692 |
| N2AB | 21748 | 65467;65468;65469 | chr2:178575967;178575966;178575965 | chr2:179440694;179440693;179440692 |
| N2A | 20821 | 62686;62687;62688 | chr2:178575967;178575966;178575965 | chr2:179440694;179440693;179440692 |
| N2B | 14324 | 43195;43196;43197 | chr2:178575967;178575966;178575965 | chr2:179440694;179440693;179440692 |
| Novex-1 | 14449 | 43570;43571;43572 | chr2:178575967;178575966;178575965 | chr2:179440694;179440693;179440692 |
| Novex-2 | 14516 | 43771;43772;43773 | chr2:178575967;178575966;178575965 | chr2:179440694;179440693;179440692 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/G | rs1194442496  |
None | 0.067 | N | 0.369 | 0.216 | 0.216624796971 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/G | rs1194442496 |
None | 0.067 | N | 0.369 | 0.216 | 0.216624796971 | gnomAD-4.0.0 | 1.31543E-05 | None | None | None | None | N | None | 2.41394E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47093E-05 | 0 | 0 |
| A/T | rs1709937178 |
None | 0.994 | N | 0.667 | 0.291 | 0.333651784274 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6125 | likely_pathogenic | 0.597 | pathogenic | -1.084 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| A/D | 0.9797 | likely_pathogenic | 0.9796 | pathogenic | -1.848 | Destabilizing | 0.988 | D | 0.767 | deleterious | N | 0.498570026 | None | None | N |
| A/E | 0.9659 | likely_pathogenic | 0.9662 | pathogenic | -1.782 | Destabilizing | 0.995 | D | 0.75 | deleterious | None | None | None | None | N |
| A/F | 0.8395 | likely_pathogenic | 0.8612 | pathogenic | -0.901 | Destabilizing | 0.998 | D | 0.813 | deleterious | None | None | None | None | N |
| A/G | 0.2101 | likely_benign | 0.2159 | benign | -1.371 | Destabilizing | 0.067 | N | 0.369 | neutral | N | 0.50517951 | None | None | N |
| A/H | 0.9679 | likely_pathogenic | 0.9671 | pathogenic | -1.773 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| A/I | 0.7691 | likely_pathogenic | 0.7853 | pathogenic | -0.139 | Destabilizing | 0.998 | D | 0.781 | deleterious | None | None | None | None | N |
| A/K | 0.9855 | likely_pathogenic | 0.987 | pathogenic | -1.566 | Destabilizing | 0.991 | D | 0.755 | deleterious | None | None | None | None | N |
| A/L | 0.7334 | likely_pathogenic | 0.7486 | pathogenic | -0.139 | Destabilizing | 0.995 | D | 0.704 | prob.neutral | None | None | None | None | N |
| A/M | 0.7843 | likely_pathogenic | 0.785 | pathogenic | -0.175 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| A/N | 0.945 | likely_pathogenic | 0.9414 | pathogenic | -1.497 | Destabilizing | 0.991 | D | 0.782 | deleterious | None | None | None | None | N |
| A/P | 0.962 | likely_pathogenic | 0.9721 | pathogenic | -0.385 | Destabilizing | 0.998 | D | 0.78 | deleterious | N | 0.487049136 | None | None | N |
| A/Q | 0.9459 | likely_pathogenic | 0.9436 | pathogenic | -1.5 | Destabilizing | 0.998 | D | 0.795 | deleterious | None | None | None | None | N |
| A/R | 0.9681 | likely_pathogenic | 0.971 | pathogenic | -1.355 | Destabilizing | 0.995 | D | 0.781 | deleterious | None | None | None | None | N |
| A/S | 0.2992 | likely_benign | 0.2653 | benign | -1.838 | Destabilizing | 0.958 | D | 0.509 | neutral | N | 0.517839376 | None | None | N |
| A/T | 0.4853 | ambiguous | 0.4521 | ambiguous | -1.665 | Destabilizing | 0.994 | D | 0.667 | neutral | N | 0.471336295 | None | None | N |
| A/V | 0.4681 | ambiguous | 0.4863 | ambiguous | -0.385 | Destabilizing | 0.979 | D | 0.611 | neutral | N | 0.444128264 | None | None | N |
| A/W | 0.972 | likely_pathogenic | 0.9752 | pathogenic | -1.482 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| A/Y | 0.8966 | likely_pathogenic | 0.9076 | pathogenic | -0.991 | Destabilizing | 1.0 | D | 0.795 | deleterious | 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.