Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29085 | 87478;87479;87480 | chr2:178558101;178558100;178558099 | chr2:179422828;179422827;179422826 |
| N2AB | 27444 | 82555;82556;82557 | chr2:178558101;178558100;178558099 | chr2:179422828;179422827;179422826 |
| N2A | 26517 | 79774;79775;79776 | chr2:178558101;178558100;178558099 | chr2:179422828;179422827;179422826 |
| N2B | 20020 | 60283;60284;60285 | chr2:178558101;178558100;178558099 | chr2:179422828;179422827;179422826 |
| Novex-1 | 20145 | 60658;60659;60660 | chr2:178558101;178558100;178558099 | chr2:179422828;179422827;179422826 |
| Novex-2 | 20212 | 60859;60860;60861 | chr2:178558101;178558100;178558099 | chr2:179422828;179422827;179422826 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs376026291  |
-1.472 | 0.942 | D | 0.688 | 0.353 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| L/F | rs376026291 |
-1.472 | 0.942 | D | 0.688 | 0.353 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| L/F | rs376026291 |
-1.472 | 0.942 | D | 0.688 | 0.353 | None | gnomAD-4.0.0 | 4.39971E-05 | None | None | None | None | I | None | 1.33494E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.84824E-05 | 0 | 1.60102E-05 |
| L/I | rs376026291 |
-0.637 | 0.014 | N | 0.35 | 0.106 | 0.26547132957 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 0 | 0 |
| L/I | rs376026291 |
-0.637 | 0.014 | N | 0.35 | 0.106 | 0.26547132957 | gnomAD-4.0.0 | 6.84178E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.87322E-05 | 0 | 0 | 0 | 0 |
| L/P | rs985791328 |
None | 0.99 | N | 0.845 | 0.714 | 0.893114649504 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.36 | ambiguous | 0.4048 | ambiguous | -1.672 | Destabilizing | 0.754 | D | 0.465 | neutral | None | None | None | None | I |
| L/C | 0.5389 | ambiguous | 0.5668 | pathogenic | -1.256 | Destabilizing | 0.994 | D | 0.753 | deleterious | None | None | None | None | I |
| L/D | 0.8876 | likely_pathogenic | 0.9094 | pathogenic | -0.604 | Destabilizing | 0.993 | D | 0.846 | deleterious | None | None | None | None | I |
| L/E | 0.6543 | likely_pathogenic | 0.6717 | pathogenic | -0.503 | Destabilizing | 0.978 | D | 0.839 | deleterious | None | None | None | None | I |
| L/F | 0.2017 | likely_benign | 0.2145 | benign | -0.943 | Destabilizing | 0.942 | D | 0.688 | prob.neutral | D | 0.536625498 | None | None | I |
| L/G | 0.6587 | likely_pathogenic | 0.7185 | pathogenic | -2.051 | Highly Destabilizing | 0.978 | D | 0.823 | deleterious | None | None | None | None | I |
| L/H | 0.5198 | ambiguous | 0.5511 | ambiguous | -1.012 | Destabilizing | 0.997 | D | 0.837 | deleterious | N | 0.512165873 | None | None | I |
| L/I | 0.0782 | likely_benign | 0.0878 | benign | -0.663 | Destabilizing | 0.014 | N | 0.35 | neutral | N | 0.521594544 | None | None | I |
| L/K | 0.5925 | likely_pathogenic | 0.6216 | pathogenic | -1.038 | Destabilizing | 0.978 | D | 0.795 | deleterious | None | None | None | None | I |
| L/M | 0.126 | likely_benign | 0.1283 | benign | -0.811 | Destabilizing | 0.956 | D | 0.712 | prob.delet. | None | None | None | None | I |
| L/N | 0.635 | likely_pathogenic | 0.7008 | pathogenic | -1.096 | Destabilizing | 0.993 | D | 0.843 | deleterious | None | None | None | None | I |
| L/P | 0.526 | ambiguous | 0.5683 | pathogenic | -0.973 | Destabilizing | 0.99 | D | 0.845 | deleterious | N | 0.511912384 | None | None | I |
| L/Q | 0.348 | ambiguous | 0.3676 | ambiguous | -1.056 | Destabilizing | 0.993 | D | 0.823 | deleterious | None | None | None | None | I |
| L/R | 0.5007 | ambiguous | 0.5224 | ambiguous | -0.682 | Destabilizing | 0.971 | D | 0.826 | deleterious | D | 0.523433273 | None | None | I |
| L/S | 0.4996 | ambiguous | 0.5617 | ambiguous | -1.838 | Destabilizing | 0.956 | D | 0.782 | deleterious | None | None | None | None | I |
| L/T | 0.3745 | ambiguous | 0.4141 | ambiguous | -1.587 | Destabilizing | 0.956 | D | 0.678 | prob.neutral | None | None | None | None | I |
| L/V | 0.0713 | likely_benign | 0.0818 | benign | -0.973 | Destabilizing | 0.014 | N | 0.341 | neutral | N | 0.490388989 | None | None | I |
| L/W | 0.4692 | ambiguous | 0.4518 | ambiguous | -0.974 | Destabilizing | 0.998 | D | 0.787 | deleterious | None | None | None | None | I |
| L/Y | 0.5341 | ambiguous | 0.5538 | ambiguous | -0.768 | Destabilizing | 0.978 | D | 0.784 | 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.