Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26423 | 79492;79493;79494 | chr2:178566865;178566864;178566863 | chr2:179431592;179431591;179431590 |
| N2AB | 24782 | 74569;74570;74571 | chr2:178566865;178566864;178566863 | chr2:179431592;179431591;179431590 |
| N2A | 23855 | 71788;71789;71790 | chr2:178566865;178566864;178566863 | chr2:179431592;179431591;179431590 |
| N2B | 17358 | 52297;52298;52299 | chr2:178566865;178566864;178566863 | chr2:179431592;179431591;179431590 |
| Novex-1 | 17483 | 52672;52673;52674 | chr2:178566865;178566864;178566863 | chr2:179431592;179431591;179431590 |
| Novex-2 | 17550 | 52873;52874;52875 | chr2:178566865;178566864;178566863 | chr2:179431592;179431591;179431590 |
| 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 | rs576203363  |
-2.538 | 0.892 | D | 0.599 | 0.602 | 0.650396906566 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| V/A | rs576203363 |
-2.538 | 0.892 | D | 0.599 | 0.602 | 0.650396906566 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07383E-04 | 0 |
| V/A | rs576203363 |
-2.538 | 0.892 | D | 0.599 | 0.602 | 0.650396906566 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| V/A | rs576203363 |
-2.538 | 0.892 | D | 0.599 | 0.602 | 0.650396906566 | gnomAD-4.0.0 | 4.95833E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08617E-06 | 2.19611E-05 | 0 |
| V/G | None | None | 0.983 | D | 0.861 | 0.789 | 0.851511300201 | gnomAD-4.0.0 | 6.8434E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65706E-05 |
| V/L | rs1706066147 |
None | 0.025 | N | 0.347 | 0.19 | 0.288727942641 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 1.96799E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs1706066147 |
None | 0.025 | N | 0.347 | 0.19 | 0.288727942641 | gnomAD-4.0.0 | 1.97259E-05 | None | None | None | None | N | None | 0 | 1.96799E-04 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6677 | likely_pathogenic | 0.6217 | pathogenic | -2.442 | Highly Destabilizing | 0.892 | D | 0.599 | neutral | D | 0.548389794 | None | None | N |
| V/C | 0.9474 | likely_pathogenic | 0.936 | pathogenic | -1.894 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | N |
| V/D | 0.9988 | likely_pathogenic | 0.9988 | pathogenic | -3.441 | Highly Destabilizing | 0.996 | D | 0.876 | deleterious | None | None | None | None | N |
| V/E | 0.9936 | likely_pathogenic | 0.9946 | pathogenic | -3.135 | Highly Destabilizing | 0.983 | D | 0.832 | deleterious | D | 0.560506567 | None | None | N |
| V/F | 0.8749 | likely_pathogenic | 0.8831 | pathogenic | -1.417 | Destabilizing | 0.975 | D | 0.725 | prob.delet. | None | None | None | None | N |
| V/G | 0.9246 | likely_pathogenic | 0.9331 | pathogenic | -3.053 | Highly Destabilizing | 0.983 | D | 0.861 | deleterious | D | 0.560506567 | None | None | N |
| V/H | 0.9982 | likely_pathogenic | 0.9984 | pathogenic | -2.935 | Highly Destabilizing | 0.999 | D | 0.842 | deleterious | None | None | None | None | N |
| V/I | 0.0879 | likely_benign | 0.0761 | benign | -0.671 | Destabilizing | 0.025 | N | 0.24 | neutral | N | 0.459110785 | None | None | N |
| V/K | 0.9958 | likely_pathogenic | 0.9965 | pathogenic | -2.133 | Highly Destabilizing | 0.987 | D | 0.834 | deleterious | None | None | None | None | N |
| V/L | 0.2604 | likely_benign | 0.2673 | benign | -0.671 | Destabilizing | 0.025 | N | 0.347 | neutral | N | 0.473237662 | None | None | N |
| V/M | 0.5149 | ambiguous | 0.5259 | ambiguous | -0.789 | Destabilizing | 0.975 | D | 0.618 | neutral | None | None | None | None | N |
| V/N | 0.9954 | likely_pathogenic | 0.9945 | pathogenic | -2.754 | Highly Destabilizing | 0.996 | D | 0.879 | deleterious | None | None | None | None | N |
| V/P | 0.9857 | likely_pathogenic | 0.985 | pathogenic | -1.241 | Destabilizing | 0.996 | D | 0.843 | deleterious | None | None | None | None | N |
| V/Q | 0.9917 | likely_pathogenic | 0.9929 | pathogenic | -2.433 | Highly Destabilizing | 0.996 | D | 0.855 | deleterious | None | None | None | None | N |
| V/R | 0.992 | likely_pathogenic | 0.9935 | pathogenic | -2.126 | Highly Destabilizing | 0.987 | D | 0.879 | deleterious | None | None | None | None | N |
| V/S | 0.9604 | likely_pathogenic | 0.9571 | pathogenic | -3.303 | Highly Destabilizing | 0.987 | D | 0.809 | deleterious | None | None | None | None | N |
| V/T | 0.796 | likely_pathogenic | 0.7559 | pathogenic | -2.839 | Highly Destabilizing | 0.916 | D | 0.607 | neutral | None | None | None | None | N |
| V/W | 0.9977 | likely_pathogenic | 0.9979 | pathogenic | -2.046 | Highly Destabilizing | 0.999 | D | 0.809 | deleterious | None | None | None | None | N |
| V/Y | 0.9933 | likely_pathogenic | 0.9933 | pathogenic | -1.691 | Destabilizing | 0.987 | D | 0.719 | 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.