Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33527 | 100804;100805;100806 | chr2:178536168;178536167;178536166 | chr2:179400895;179400894;179400893 |
| N2AB | 31886 | 95881;95882;95883 | chr2:178536168;178536167;178536166 | chr2:179400895;179400894;179400893 |
| N2A | 30959 | 93100;93101;93102 | chr2:178536168;178536167;178536166 | chr2:179400895;179400894;179400893 |
| N2B | 24462 | 73609;73610;73611 | chr2:178536168;178536167;178536166 | chr2:179400895;179400894;179400893 |
| Novex-1 | 24587 | 73984;73985;73986 | chr2:178536168;178536167;178536166 | chr2:179400895;179400894;179400893 |
| Novex-2 | 24654 | 74185;74186;74187 | chr2:178536168;178536167;178536166 | chr2:179400895;179400894;179400893 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs2278196  |
-0.388 | 0.774 | N | 0.285 | 0.207 | None | gnomAD-2.1.1 | 3.23055E-02 | None | None | None | None | N | None | 7.07184E-02 | 3.01533E-02 | None | 2.57652E-02 | 1.54713E-01 | None | 1.37435E-02 | None | 3.0024E-03 | 1.78054E-02 | 3.04054E-02 |
| V/I | rs2278196 |
-0.388 | 0.774 | N | 0.285 | 0.207 | None | gnomAD-3.1.2 | 3.7948E-02 | None | None | None | None | N | None | 7.01102E-02 | 3.77606E-02 | 4.38597E-03 | 2.8291E-02 | 1.46059E-01 | None | 1.88501E-03 | 5.06329E-02 | 1.80409E-02 | 1.2443E-02 | 5.30593E-02 |
| V/I | rs2278196 |
-0.388 | 0.774 | N | 0.285 | 0.207 | None | 1000 genomes | 6.54952E-02 | None | None | None | None | N | None | 8.47E-02 | 3.6E-02 | None | None | 1.488E-01 | 2.98E-02 | None | None | None | 1.12E-02 | None |
| V/I | rs2278196 |
-0.388 | 0.774 | N | 0.285 | 0.207 | None | gnomAD-4.0.0 | 2.53438E-02 | None | None | None | None | N | None | 7.02321E-02 | 3.31887E-02 | None | 2.56826E-02 | 1.61574E-01 | None | 2.92233E-03 | 7.9069E-02 | 1.84834E-02 | 1.35735E-02 | 3.07727E-02 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.9016 | likely_pathogenic | 0.8797 | pathogenic | -1.865 | Destabilizing | 0.997 | D | 0.627 | neutral | D | 0.554815934 | None | None | N |
| V/C | 0.9557 | likely_pathogenic | 0.9497 | pathogenic | -0.987 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| V/D | 0.998 | likely_pathogenic | 0.9975 | pathogenic | -2.257 | Highly Destabilizing | 1.0 | D | 0.842 | deleterious | D | 0.587863678 | None | None | N |
| V/E | 0.9912 | likely_pathogenic | 0.9896 | pathogenic | -2.156 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| V/F | 0.8199 | likely_pathogenic | 0.7785 | pathogenic | -1.287 | Destabilizing | 1.0 | D | 0.798 | deleterious | D | 0.577989113 | None | None | N |
| V/G | 0.9611 | likely_pathogenic | 0.9549 | pathogenic | -2.262 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | D | 0.604115203 | None | None | N |
| V/H | 0.9968 | likely_pathogenic | 0.9961 | pathogenic | -1.924 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| V/I | 0.0825 | likely_benign | 0.073 | benign | -0.805 | Destabilizing | 0.774 | D | 0.285 | neutral | N | 0.447025001 | None | None | N |
| V/K | 0.991 | likely_pathogenic | 0.9896 | pathogenic | -1.63 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| V/L | 0.574 | likely_pathogenic | 0.5254 | ambiguous | -0.805 | Destabilizing | 0.96 | D | 0.637 | neutral | D | 0.560318602 | None | None | N |
| V/M | 0.5942 | likely_pathogenic | 0.5769 | pathogenic | -0.511 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| V/N | 0.9905 | likely_pathogenic | 0.9884 | pathogenic | -1.542 | Destabilizing | 0.999 | D | 0.862 | deleterious | None | None | None | None | N |
| V/P | 0.9856 | likely_pathogenic | 0.9845 | pathogenic | -1.13 | Destabilizing | 0.999 | D | 0.837 | deleterious | None | None | None | None | N |
| V/Q | 0.9863 | likely_pathogenic | 0.9842 | pathogenic | -1.6 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| V/R | 0.9869 | likely_pathogenic | 0.9844 | pathogenic | -1.2 | Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| V/S | 0.9646 | likely_pathogenic | 0.9563 | pathogenic | -2.011 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| V/T | 0.8548 | likely_pathogenic | 0.834 | pathogenic | -1.803 | Destabilizing | 0.997 | D | 0.723 | prob.delet. | None | None | None | None | N |
| V/W | 0.9966 | likely_pathogenic | 0.9958 | pathogenic | -1.668 | Destabilizing | 1.0 | D | 0.846 | deleterious | None | None | None | None | N |
| V/Y | 0.9891 | likely_pathogenic | 0.9859 | pathogenic | -1.342 | Destabilizing | 1.0 | D | 0.797 | 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.