Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30626 | 92101;92102;92103 | chr2:178549846;178549845;178549844 | chr2:179414573;179414572;179414571 |
| N2AB | 28985 | 87178;87179;87180 | chr2:178549846;178549845;178549844 | chr2:179414573;179414572;179414571 |
| N2A | 28058 | 84397;84398;84399 | chr2:178549846;178549845;178549844 | chr2:179414573;179414572;179414571 |
| N2B | 21561 | 64906;64907;64908 | chr2:178549846;178549845;178549844 | chr2:179414573;179414572;179414571 |
| Novex-1 | 21686 | 65281;65282;65283 | chr2:178549846;178549845;178549844 | chr2:179414573;179414572;179414571 |
| Novex-2 | 21753 | 65482;65483;65484 | chr2:178549846;178549845;178549844 | chr2:179414573;179414572;179414571 |
| 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/R | None | None | 1.0 | N | 0.819 | 0.516 | 0.490701487448 | gnomAD-4.0.0 | 7.0044E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.12875E-07 | 0 | 0 |
| P/S | rs888849578  |
-0.547 | 1.0 | N | 0.807 | 0.432 | 0.387202362727 | gnomAD-2.1.1 | 4.56E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.94E-05 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs888849578 |
-0.547 | 1.0 | N | 0.807 | 0.432 | 0.387202362727 | gnomAD-4.0.0 | 1.69052E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.80505E-05 | 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 | 0.2044 | likely_benign | 0.2551 | benign | -0.44 | Destabilizing | 1.0 | D | 0.77 | deleterious | N | 0.494841864 | None | None | I |
| P/C | 0.7007 | likely_pathogenic | 0.7949 | pathogenic | -0.794 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
| P/D | 0.5431 | ambiguous | 0.6467 | pathogenic | -0.114 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | I |
| P/E | 0.4434 | ambiguous | 0.5367 | ambiguous | -0.206 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| P/F | 0.7795 | likely_pathogenic | 0.8665 | pathogenic | -0.536 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| P/G | 0.5184 | ambiguous | 0.617 | pathogenic | -0.574 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | I |
| P/H | 0.3604 | ambiguous | 0.4804 | ambiguous | 0.003 | Stabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| P/I | 0.6751 | likely_pathogenic | 0.7517 | pathogenic | -0.227 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | I |
| P/K | 0.457 | ambiguous | 0.5689 | pathogenic | -0.427 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | I |
| P/L | 0.3326 | likely_benign | 0.4227 | ambiguous | -0.227 | Destabilizing | 1.0 | D | 0.813 | deleterious | N | 0.515509651 | None | None | I |
| P/M | 0.6011 | likely_pathogenic | 0.686 | pathogenic | -0.494 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | I |
| P/N | 0.4607 | ambiguous | 0.5583 | ambiguous | -0.256 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | I |
| P/Q | 0.3003 | likely_benign | 0.3854 | ambiguous | -0.447 | Destabilizing | 1.0 | D | 0.795 | deleterious | N | 0.488120368 | None | None | I |
| P/R | 0.3314 | likely_benign | 0.4527 | ambiguous | 0.056 | Stabilizing | 1.0 | D | 0.819 | deleterious | N | 0.515517013 | None | None | I |
| P/S | 0.2827 | likely_benign | 0.3684 | ambiguous | -0.658 | Destabilizing | 1.0 | D | 0.807 | deleterious | N | 0.473294569 | None | None | I |
| P/T | 0.2587 | likely_benign | 0.3256 | benign | -0.644 | Destabilizing | 1.0 | D | 0.802 | deleterious | N | 0.491069655 | None | None | I |
| P/V | 0.5013 | ambiguous | 0.5834 | pathogenic | -0.265 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | I |
| P/W | 0.8801 | likely_pathogenic | 0.9382 | pathogenic | -0.595 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | I |
| P/Y | 0.7386 | likely_pathogenic | 0.8358 | pathogenic | -0.317 | Destabilizing | 1.0 | D | 0.794 | deleterious | 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.