Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23903 | 71932;71933;71934 | chr2:178574425;178574424;178574423 | chr2:179439152;179439151;179439150 |
| N2AB | 22262 | 67009;67010;67011 | chr2:178574425;178574424;178574423 | chr2:179439152;179439151;179439150 |
| N2A | 21335 | 64228;64229;64230 | chr2:178574425;178574424;178574423 | chr2:179439152;179439151;179439150 |
| N2B | 14838 | 44737;44738;44739 | chr2:178574425;178574424;178574423 | chr2:179439152;179439151;179439150 |
| Novex-1 | 14963 | 45112;45113;45114 | chr2:178574425;178574424;178574423 | chr2:179439152;179439151;179439150 |
| Novex-2 | 15030 | 45313;45314;45315 | chr2:178574425;178574424;178574423 | chr2:179439152;179439151;179439150 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/E | None | None | 1.0 | D | 0.837 | 0.787 | 0.820753909017 | gnomAD-4.0.0 | 6.84317E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99577E-07 | 0 | 0 |
| A/G | rs759693046  |
-2.72 | 1.0 | D | 0.643 | 0.771 | 0.713883852837 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.9E-06 | 0 |
| A/G | rs759693046 |
-2.72 | 1.0 | D | 0.643 | 0.771 | 0.713883852837 | gnomAD-4.0.0 | 1.36863E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99577E-07 | 1.15977E-05 | 0 |
| A/T | rs767300259 |
-2.0 | 1.0 | D | 0.797 | 0.838 | 0.713429338685 | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | N | None | 2.48036E-04 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| A/T | rs767300259 |
-2.0 | 1.0 | D | 0.797 | 0.838 | 0.713429338685 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 1.68886E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs767300259 |
-2.0 | 1.0 | D | 0.797 | 0.838 | 0.713429338685 | gnomAD-4.0.0 | 6.19834E-06 | None | None | None | None | N | None | 1.20154E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.09844E-05 | 0 |
| A/V | None | None | 1.0 | D | 0.715 | 0.762 | 0.756616091254 | gnomAD-4.0.0 | 1.36863E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79915E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.8169 | likely_pathogenic | 0.85 | pathogenic | -1.841 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| A/D | 0.9979 | likely_pathogenic | 0.9987 | pathogenic | -2.934 | Highly Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| A/E | 0.9956 | likely_pathogenic | 0.9973 | pathogenic | -2.696 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | D | 0.664770898 | None | None | N |
| A/F | 0.9945 | likely_pathogenic | 0.9965 | pathogenic | -0.729 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| A/G | 0.4937 | ambiguous | 0.558 | ambiguous | -2.265 | Highly Destabilizing | 1.0 | D | 0.643 | neutral | D | 0.615068021 | None | None | N |
| A/H | 0.9977 | likely_pathogenic | 0.9986 | pathogenic | -2.219 | Highly Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| A/I | 0.9751 | likely_pathogenic | 0.9868 | pathogenic | -0.563 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| A/K | 0.999 | likely_pathogenic | 0.9994 | pathogenic | -1.536 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| A/L | 0.9388 | likely_pathogenic | 0.9536 | pathogenic | -0.563 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| A/M | 0.96 | likely_pathogenic | 0.9744 | pathogenic | -1.082 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| A/N | 0.9934 | likely_pathogenic | 0.9965 | pathogenic | -2.019 | Highly Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| A/P | 0.9832 | likely_pathogenic | 0.9912 | pathogenic | -0.95 | Destabilizing | 1.0 | D | 0.846 | deleterious | D | 0.638829178 | None | None | N |
| A/Q | 0.9904 | likely_pathogenic | 0.9933 | pathogenic | -1.715 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| A/R | 0.9951 | likely_pathogenic | 0.9964 | pathogenic | -1.625 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| A/S | 0.3054 | likely_benign | 0.3743 | ambiguous | -2.384 | Highly Destabilizing | 1.0 | D | 0.634 | neutral | D | 0.591942637 | None | None | N |
| A/T | 0.656 | likely_pathogenic | 0.7841 | pathogenic | -2.038 | Highly Destabilizing | 1.0 | D | 0.797 | deleterious | D | 0.631692794 | None | None | N |
| A/V | 0.8373 | likely_pathogenic | 0.9051 | pathogenic | -0.95 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | D | 0.637820156 | None | None | N |
| A/W | 0.9994 | likely_pathogenic | 0.9996 | pathogenic | -1.406 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| A/Y | 0.9978 | likely_pathogenic | 0.9985 | pathogenic | -1.116 | Destabilizing | 1.0 | D | 0.865 | 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.