Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35216 | 105871;105872;105873 | chr2:178530969;178530968;178530967 | chr2:179395696;179395695;179395694 |
| N2AB | 33575 | 100948;100949;100950 | chr2:178530969;178530968;178530967 | chr2:179395696;179395695;179395694 |
| N2A | 32648 | 98167;98168;98169 | chr2:178530969;178530968;178530967 | chr2:179395696;179395695;179395694 |
| N2B | 26151 | 78676;78677;78678 | chr2:178530969;178530968;178530967 | chr2:179395696;179395695;179395694 |
| Novex-1 | 26276 | 79051;79052;79053 | chr2:178530969;178530968;178530967 | chr2:179395696;179395695;179395694 |
| Novex-2 | 26343 | 79252;79253;79254 | chr2:178530969;178530968;178530967 | chr2:179395696;179395695;179395694 |
| 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 | None | None | 0.999 | D | 0.809 | 0.348 | 0.50857664894 | gnomAD-4.0.0 | 1.59089E-06 | None | None | None | None | N | None | 0 | 2.28624E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/P | rs1575223863  |
None | 1.0 | D | 0.91 | 0.742 | 0.874903976484 | gnomAD-4.0.0 | 2.73655E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51889E-05 | None | 0 | 0 | 2.69818E-06 | 0 | 0 |
| L/Q | None | None | 1.0 | D | 0.916 | 0.671 | 0.856284893043 | gnomAD-4.0.0 | 6.84139E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99392E-07 | 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 | 0.9373 | likely_pathogenic | 0.9573 | pathogenic | -2.8 | Highly Destabilizing | 0.998 | D | 0.758 | deleterious | None | None | None | None | N |
| L/C | 0.9413 | likely_pathogenic | 0.9498 | pathogenic | -2.299 | Highly Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| L/D | 0.9993 | likely_pathogenic | 0.9996 | pathogenic | -3.346 | Highly Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| L/E | 0.9951 | likely_pathogenic | 0.9968 | pathogenic | -3.029 | Highly Destabilizing | 1.0 | D | 0.902 | deleterious | None | None | None | None | N |
| L/F | 0.5174 | ambiguous | 0.7039 | pathogenic | -1.664 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| L/G | 0.9907 | likely_pathogenic | 0.9945 | pathogenic | -3.427 | Highly Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| L/H | 0.9883 | likely_pathogenic | 0.9928 | pathogenic | -3.08 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| L/I | 0.1735 | likely_benign | 0.2273 | benign | -0.92 | Destabilizing | 0.91 | D | 0.368 | neutral | None | None | None | None | N |
| L/K | 0.9914 | likely_pathogenic | 0.9938 | pathogenic | -2.039 | Highly Destabilizing | 1.0 | D | 0.912 | deleterious | None | None | None | None | N |
| L/M | 0.3186 | likely_benign | 0.3736 | ambiguous | -1.204 | Destabilizing | 0.999 | D | 0.809 | deleterious | D | 0.536608052 | None | None | N |
| L/N | 0.9967 | likely_pathogenic | 0.9975 | pathogenic | -2.7 | Highly Destabilizing | 1.0 | D | 0.914 | deleterious | None | None | None | None | N |
| L/P | 0.9955 | likely_pathogenic | 0.9973 | pathogenic | -1.536 | Destabilizing | 1.0 | D | 0.91 | deleterious | D | 0.548724826 | None | None | N |
| L/Q | 0.9798 | likely_pathogenic | 0.9856 | pathogenic | -2.368 | Highly Destabilizing | 1.0 | D | 0.916 | deleterious | D | 0.548724826 | None | None | N |
| L/R | 0.9786 | likely_pathogenic | 0.9854 | pathogenic | -2.061 | Highly Destabilizing | 1.0 | D | 0.915 | deleterious | D | 0.548724826 | None | None | N |
| L/S | 0.9921 | likely_pathogenic | 0.9947 | pathogenic | -3.361 | Highly Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| L/T | 0.9678 | likely_pathogenic | 0.9757 | pathogenic | -2.87 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| L/V | 0.2042 | likely_benign | 0.2628 | benign | -1.536 | Destabilizing | 0.981 | D | 0.659 | neutral | N | 0.471749221 | None | None | N |
| L/W | 0.9446 | likely_pathogenic | 0.9757 | pathogenic | -2.062 | Highly Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| L/Y | 0.9633 | likely_pathogenic | 0.9813 | pathogenic | -1.844 | Destabilizing | 1.0 | D | 0.873 | 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.