Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30627 | 92104;92105;92106 | chr2:178549843;178549842;178549841 | chr2:179414570;179414569;179414568 |
| N2AB | 28986 | 87181;87182;87183 | chr2:178549843;178549842;178549841 | chr2:179414570;179414569;179414568 |
| N2A | 28059 | 84400;84401;84402 | chr2:178549843;178549842;178549841 | chr2:179414570;179414569;179414568 |
| N2B | 21562 | 64909;64910;64911 | chr2:178549843;178549842;178549841 | chr2:179414570;179414569;179414568 |
| Novex-1 | 21687 | 65284;65285;65286 | chr2:178549843;178549842;178549841 | chr2:179414570;179414569;179414568 |
| Novex-2 | 21754 | 65485;65486;65487 | chr2:178549843;178549842;178549841 | chr2:179414570;179414569;179414568 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | None | None | 0.031 | N | 0.248 | 0.089 | 0.272639205421 | gnomAD-4.0.0 | 1.39944E-06 | None | None | None | None | N | None | 0 | 2.50426E-05 | None | 0 | 0 | None | 0 | 0 | 9.12267E-07 | 0 | 0 |
| I/T | rs747482573  |
-2.712 | 0.98 | N | 0.775 | 0.549 | 0.661029647469 | gnomAD-2.1.1 | 8.78E-06 | None | None | None | None | N | None | 0 | 3.28E-05 | None | 0 | 5.78E-05 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs747482573 |
-2.712 | 0.98 | N | 0.775 | 0.549 | 0.661029647469 | gnomAD-4.0.0 | 3.34401E-06 | None | None | None | None | N | None | 0 | 2.52551E-05 | None | 0 | 2.803E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs535151633 |
-1.286 | 0.689 | N | 0.486 | 0.148 | 0.390531646278 | gnomAD-2.1.1 | 2.34E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.66184E-04 | None | 0 | None | 0 | 0 | 1.56201E-04 |
| I/V | rs535151633 |
-1.286 | 0.689 | N | 0.486 | 0.148 | 0.390531646278 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.9253E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs535151633 |
-1.286 | 0.689 | N | 0.486 | 0.148 | 0.390531646278 | gnomAD-4.0.0 | 1.13827E-05 | None | None | None | None | N | None | 6.80531E-05 | 0 | None | 0 | 1.79759E-04 | None | 0 | 0 | 0 | 2.34681E-05 | 4.92837E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8816 | likely_pathogenic | 0.9007 | pathogenic | -2.265 | Highly Destabilizing | 0.985 | D | 0.707 | prob.neutral | None | None | None | None | N |
| I/C | 0.924 | likely_pathogenic | 0.934 | pathogenic | -1.486 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| I/D | 0.9967 | likely_pathogenic | 0.9975 | pathogenic | -2.625 | Highly Destabilizing | 0.999 | D | 0.829 | deleterious | None | None | None | None | N |
| I/E | 0.9914 | likely_pathogenic | 0.9928 | pathogenic | -2.345 | Highly Destabilizing | 0.999 | D | 0.829 | deleterious | None | None | None | None | N |
| I/F | 0.4759 | ambiguous | 0.5803 | pathogenic | -1.211 | Destabilizing | 0.991 | D | 0.758 | deleterious | None | None | None | None | N |
| I/G | 0.9834 | likely_pathogenic | 0.9876 | pathogenic | -2.856 | Highly Destabilizing | 0.999 | D | 0.833 | deleterious | None | None | None | None | N |
| I/H | 0.9871 | likely_pathogenic | 0.9907 | pathogenic | -2.483 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| I/K | 0.9822 | likely_pathogenic | 0.9864 | pathogenic | -1.706 | Destabilizing | 0.998 | D | 0.833 | deleterious | N | 0.500793346 | None | None | N |
| I/L | 0.1049 | likely_benign | 0.1222 | benign | -0.538 | Destabilizing | 0.031 | N | 0.248 | neutral | N | 0.376632969 | None | None | N |
| I/M | 0.1834 | likely_benign | 0.2136 | benign | -0.592 | Destabilizing | 0.989 | D | 0.705 | prob.neutral | N | 0.473281342 | None | None | N |
| I/N | 0.9626 | likely_pathogenic | 0.9702 | pathogenic | -2.177 | Highly Destabilizing | 0.999 | D | 0.831 | deleterious | None | None | None | None | N |
| I/P | 0.9354 | likely_pathogenic | 0.9386 | pathogenic | -1.096 | Destabilizing | 0.999 | D | 0.827 | deleterious | None | None | None | None | N |
| I/Q | 0.98 | likely_pathogenic | 0.9839 | pathogenic | -1.914 | Destabilizing | 0.999 | D | 0.842 | deleterious | None | None | None | None | N |
| I/R | 0.9771 | likely_pathogenic | 0.9826 | pathogenic | -1.674 | Destabilizing | 0.998 | D | 0.829 | deleterious | N | 0.500793346 | None | None | N |
| I/S | 0.9506 | likely_pathogenic | 0.9594 | pathogenic | -2.847 | Highly Destabilizing | 0.999 | D | 0.783 | deleterious | None | None | None | None | N |
| I/T | 0.919 | likely_pathogenic | 0.932 | pathogenic | -2.408 | Highly Destabilizing | 0.98 | D | 0.775 | deleterious | N | 0.482182112 | None | None | N |
| I/V | 0.0951 | likely_benign | 0.0996 | benign | -1.096 | Destabilizing | 0.689 | D | 0.486 | neutral | N | 0.409577681 | None | None | N |
| I/W | 0.9814 | likely_pathogenic | 0.9885 | pathogenic | -1.66 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| I/Y | 0.9493 | likely_pathogenic | 0.9649 | pathogenic | -1.319 | Destabilizing | 0.999 | D | 0.727 | 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.