Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30711 | 92356;92357;92358 | chr2:178549591;178549590;178549589 | chr2:179414318;179414317;179414316 |
| N2AB | 29070 | 87433;87434;87435 | chr2:178549591;178549590;178549589 | chr2:179414318;179414317;179414316 |
| N2A | 28143 | 84652;84653;84654 | chr2:178549591;178549590;178549589 | chr2:179414318;179414317;179414316 |
| N2B | 21646 | 65161;65162;65163 | chr2:178549591;178549590;178549589 | chr2:179414318;179414317;179414316 |
| Novex-1 | 21771 | 65536;65537;65538 | chr2:178549591;178549590;178549589 | chr2:179414318;179414317;179414316 |
| Novex-2 | 21838 | 65737;65738;65739 | chr2:178549591;178549590;178549589 | chr2:179414318;179414317;179414316 |
| 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/A | None | None | 0.799 | N | 0.563 | 0.364 | 0.510346895759 | gnomAD-4.0.0 | 6.00161E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.56251E-06 | 0 | 0 |
| V/L | rs747122  |
0.365 | 0.451 | N | 0.408 | 0.208 | 0.279370189704 | gnomAD-2.1.1 | 8.1E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11383E-04 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs747122 |
0.365 | 0.451 | N | 0.408 | 0.208 | 0.279370189704 | gnomAD-4.0.0 | 4.79238E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.5124E-04 | None | 0 | 0 | 9.0008E-07 | 0 | 0 |
| V/M | rs747122 |
0.169 | 0.966 | N | 0.601 | 0.226 | None | gnomAD-2.1.1 | 9.35053E-02 | None | None | None | None | N | None | 2.56101E-01 | 2.06017E-01 | None | 3.52987E-02 | 2.76212E-02 | None | 1.82074E-01 | None | 5.71589E-02 | 3.30381E-02 | 6.708E-02 |
| V/M | rs747122 |
0.169 | 0.966 | N | 0.601 | 0.226 | None | gnomAD-3.1.2 | 1.14218E-01 | None | None | None | None | N | None | 2.55342E-01 | 1.74984E-01 | 4.93421E-02 | 3.60231E-02 | 2.44513E-02 | None | 5.88014E-02 | 8.86076E-02 | 3.14815E-02 | 1.777E-01 | 9.00383E-02 |
| V/M | rs747122 |
0.169 | 0.966 | N | 0.601 | 0.226 | None | 1000 genomes | 1.5016E-01 | None | None | None | None | N | None | 2.731E-01 | 1.787E-01 | None | None | 2.48E-02 | 4.87E-02 | None | None | None | 1.973E-01 | None |
| V/M | rs747122 |
0.169 | 0.966 | N | 0.601 | 0.226 | None | gnomAD-4.0.0 | 5.89209E-02 | None | None | None | None | N | None | 2.61695E-01 | 1.96786E-01 | None | 3.62696E-02 | 1.50488E-02 | None | 5.88529E-02 | 5.91345E-02 | 3.19641E-02 | 1.74096E-01 | 6.66037E-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 | 0.1991 | likely_benign | 0.2619 | benign | -1.566 | Destabilizing | 0.799 | D | 0.563 | neutral | N | 0.491991027 | None | None | N |
| V/C | 0.7108 | likely_pathogenic | 0.7527 | pathogenic | -1.009 | Destabilizing | 0.998 | D | 0.712 | prob.delet. | None | None | None | None | N |
| V/D | 0.7964 | likely_pathogenic | 0.8888 | pathogenic | -2.001 | Highly Destabilizing | 0.991 | D | 0.831 | deleterious | None | None | None | None | N |
| V/E | 0.5623 | ambiguous | 0.6679 | pathogenic | -1.774 | Destabilizing | 0.989 | D | 0.747 | deleterious | N | 0.51136273 | None | None | N |
| V/F | 0.2585 | likely_benign | 0.3525 | ambiguous | -0.894 | Destabilizing | 0.037 | N | 0.473 | neutral | None | None | None | None | N |
| V/G | 0.4937 | ambiguous | 0.6345 | pathogenic | -2.083 | Highly Destabilizing | 0.966 | D | 0.766 | deleterious | D | 0.523226014 | None | None | N |
| V/H | 0.7431 | likely_pathogenic | 0.8246 | pathogenic | -1.735 | Destabilizing | 0.998 | D | 0.819 | deleterious | None | None | None | None | N |
| V/I | 0.0744 | likely_benign | 0.0856 | benign | -0.135 | Destabilizing | 0.066 | N | 0.204 | neutral | None | None | None | None | N |
| V/K | 0.5363 | ambiguous | 0.6392 | pathogenic | -1.261 | Destabilizing | 0.991 | D | 0.755 | deleterious | None | None | None | None | N |
| V/L | 0.2039 | likely_benign | 0.3095 | benign | -0.135 | Destabilizing | 0.451 | N | 0.408 | neutral | N | 0.479834573 | None | None | N |
| V/M | 0.1342 | likely_benign | 0.1669 | benign | -0.172 | Destabilizing | 0.966 | D | 0.601 | neutral | N | 0.468584081 | None | None | N |
| V/N | 0.6112 | likely_pathogenic | 0.7611 | pathogenic | -1.653 | Destabilizing | 0.991 | D | 0.823 | deleterious | None | None | None | None | N |
| V/P | 0.9515 | likely_pathogenic | 0.9792 | pathogenic | -0.584 | Destabilizing | 0.991 | D | 0.763 | deleterious | None | None | None | None | N |
| V/Q | 0.4918 | ambiguous | 0.5897 | pathogenic | -1.465 | Destabilizing | 0.991 | D | 0.771 | deleterious | None | None | None | None | N |
| V/R | 0.4947 | ambiguous | 0.5864 | pathogenic | -1.198 | Destabilizing | 0.991 | D | 0.819 | deleterious | None | None | None | None | N |
| V/S | 0.4023 | ambiguous | 0.5363 | ambiguous | -2.247 | Highly Destabilizing | 0.974 | D | 0.686 | prob.delet. | None | None | None | None | N |
| V/T | 0.1873 | likely_benign | 0.2436 | benign | -1.864 | Destabilizing | 0.915 | D | 0.625 | neutral | None | None | None | None | N |
| V/W | 0.8903 | likely_pathogenic | 0.9396 | pathogenic | -1.366 | Destabilizing | 0.998 | D | 0.815 | deleterious | None | None | None | None | N |
| V/Y | 0.7063 | likely_pathogenic | 0.8016 | pathogenic | -0.904 | Destabilizing | 0.903 | D | 0.716 | prob.delet. | 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.