Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20517 | 61774;61775;61776 | chr2:178590176;178590175;178590174 | chr2:179454903;179454902;179454901 |
| N2AB | 18876 | 56851;56852;56853 | chr2:178590176;178590175;178590174 | chr2:179454903;179454902;179454901 |
| N2A | 17949 | 54070;54071;54072 | chr2:178590176;178590175;178590174 | chr2:179454903;179454902;179454901 |
| N2B | 11452 | 34579;34580;34581 | chr2:178590176;178590175;178590174 | chr2:179454903;179454902;179454901 |
| Novex-1 | 11577 | 34954;34955;34956 | chr2:178590176;178590175;178590174 | chr2:179454903;179454902;179454901 |
| Novex-2 | 11644 | 35155;35156;35157 | chr2:178590176;178590175;178590174 | chr2:179454903;179454902;179454901 |
| 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/M | rs1576082826  |
None | 0.982 | N | 0.63 | 0.361 | 0.624520489576 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/M | rs1576082826 |
None | 0.982 | N | 0.63 | 0.361 | 0.624520489576 | gnomAD-4.0.0 | 6.57678E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47119E-05 | 0 | 0 |
| L/S | rs1270401889 |
-2.786 | 0.991 | D | 0.702 | 0.584 | 0.866228988304 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 2.92E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/S | rs1270401889 |
-2.786 | 0.991 | D | 0.702 | 0.584 | 0.866228988304 | gnomAD-4.0.0 | 1.59519E-06 | None | None | None | None | N | None | 0 | 2.29421E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.479 | ambiguous | 0.586 | pathogenic | -2.205 | Highly Destabilizing | 0.91 | D | 0.479 | neutral | None | None | None | None | N |
| L/C | 0.7221 | likely_pathogenic | 0.7895 | pathogenic | -1.496 | Destabilizing | 0.999 | D | 0.676 | prob.neutral | None | None | None | None | N |
| L/D | 0.9513 | likely_pathogenic | 0.9744 | pathogenic | -1.928 | Destabilizing | 0.998 | D | 0.789 | deleterious | None | None | None | None | N |
| L/E | 0.818 | likely_pathogenic | 0.8886 | pathogenic | -1.728 | Destabilizing | 0.993 | D | 0.775 | deleterious | None | None | None | None | N |
| L/F | 0.2635 | likely_benign | 0.2973 | benign | -1.289 | Destabilizing | 0.982 | D | 0.6 | neutral | D | 0.539049728 | None | None | N |
| L/G | 0.8422 | likely_pathogenic | 0.9045 | pathogenic | -2.706 | Highly Destabilizing | 0.993 | D | 0.762 | deleterious | None | None | None | None | N |
| L/H | 0.6942 | likely_pathogenic | 0.7911 | pathogenic | -1.865 | Destabilizing | 0.999 | D | 0.757 | deleterious | None | None | None | None | N |
| L/I | 0.096 | likely_benign | 0.1042 | benign | -0.784 | Destabilizing | 0.06 | N | 0.408 | neutral | None | None | None | None | N |
| L/K | 0.7979 | likely_pathogenic | 0.8796 | pathogenic | -1.628 | Destabilizing | 0.993 | D | 0.715 | prob.delet. | None | None | None | None | N |
| L/M | 0.1553 | likely_benign | 0.1684 | benign | -0.736 | Destabilizing | 0.982 | D | 0.63 | neutral | N | 0.501023378 | None | None | N |
| L/N | 0.8229 | likely_pathogenic | 0.8958 | pathogenic | -1.9 | Destabilizing | 0.998 | D | 0.781 | deleterious | None | None | None | None | N |
| L/P | 0.6647 | likely_pathogenic | 0.7713 | pathogenic | -1.236 | Destabilizing | 0.998 | D | 0.791 | deleterious | None | None | None | None | N |
| L/Q | 0.5963 | likely_pathogenic | 0.7145 | pathogenic | -1.779 | Destabilizing | 0.998 | D | 0.738 | prob.delet. | None | None | None | None | N |
| L/R | 0.7323 | likely_pathogenic | 0.828 | pathogenic | -1.345 | Destabilizing | 0.998 | D | 0.744 | deleterious | None | None | None | None | N |
| L/S | 0.7304 | likely_pathogenic | 0.8369 | pathogenic | -2.636 | Highly Destabilizing | 0.991 | D | 0.702 | prob.neutral | D | 0.535763857 | None | None | N |
| L/T | 0.4469 | ambiguous | 0.5771 | pathogenic | -2.278 | Highly Destabilizing | 0.986 | D | 0.629 | neutral | None | None | None | None | N |
| L/V | 0.1164 | likely_benign | 0.1266 | benign | -1.236 | Destabilizing | 0.046 | N | 0.282 | neutral | N | 0.465338616 | None | None | N |
| L/W | 0.5822 | likely_pathogenic | 0.6323 | pathogenic | -1.507 | Destabilizing | 0.999 | D | 0.69 | prob.neutral | D | 0.548134121 | None | None | N |
| L/Y | 0.694 | likely_pathogenic | 0.7543 | pathogenic | -1.228 | Destabilizing | 0.998 | D | 0.705 | prob.neutral | 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.