Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19544 | 58855;58856;58857 | chr2:178593670;178593669;178593668 | chr2:179458397;179458396;179458395 |
| N2AB | 17903 | 53932;53933;53934 | chr2:178593670;178593669;178593668 | chr2:179458397;179458396;179458395 |
| N2A | 16976 | 51151;51152;51153 | chr2:178593670;178593669;178593668 | chr2:179458397;179458396;179458395 |
| N2B | 10479 | 31660;31661;31662 | chr2:178593670;178593669;178593668 | chr2:179458397;179458396;179458395 |
| Novex-1 | 10604 | 32035;32036;32037 | chr2:178593670;178593669;178593668 | chr2:179458397;179458396;179458395 |
| Novex-2 | 10671 | 32236;32237;32238 | chr2:178593670;178593669;178593668 | chr2:179458397;179458396;179458395 |
| 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/P | rs373353480  |
-1.698 | 1.0 | D | 0.827 | 0.912 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| L/P | rs373353480 |
-1.698 | 1.0 | D | 0.827 | 0.912 | None | gnomAD-4.0.0 | 8.97355E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.67585E-05 | 0 | 0 |
| L/V | rs772132591 |
-1.672 | 0.999 | D | 0.835 | 0.699 | 0.764855773497 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| L/V | rs772132591 |
-1.672 | 0.999 | D | 0.835 | 0.699 | 0.764855773497 | gnomAD-4.0.0 | 4.1066E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.95717E-05 | 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 | 0.9764 | likely_pathogenic | 0.9682 | pathogenic | -2.549 | Highly Destabilizing | 0.999 | D | 0.808 | deleterious | None | None | None | None | N |
| L/C | 0.9598 | likely_pathogenic | 0.9479 | pathogenic | -1.745 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| L/D | 0.9993 | likely_pathogenic | 0.999 | pathogenic | -2.389 | Highly Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| L/E | 0.9972 | likely_pathogenic | 0.9963 | pathogenic | -2.237 | Highly Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| L/F | 0.8508 | likely_pathogenic | 0.8274 | pathogenic | -1.601 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| L/G | 0.9932 | likely_pathogenic | 0.9918 | pathogenic | -3.046 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| L/H | 0.9918 | likely_pathogenic | 0.9896 | pathogenic | -2.264 | Highly Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| L/I | 0.3787 | ambiguous | 0.3015 | benign | -1.153 | Destabilizing | 0.999 | D | 0.826 | deleterious | D | 0.640750755 | None | None | N |
| L/K | 0.9938 | likely_pathogenic | 0.9924 | pathogenic | -1.94 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| L/M | 0.5435 | ambiguous | 0.5019 | ambiguous | -0.941 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| L/N | 0.9925 | likely_pathogenic | 0.9911 | pathogenic | -2.034 | Highly Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| L/P | 0.9923 | likely_pathogenic | 0.987 | pathogenic | -1.595 | Destabilizing | 1.0 | D | 0.827 | deleterious | D | 0.658586355 | None | None | N |
| L/Q | 0.9892 | likely_pathogenic | 0.9857 | pathogenic | -2.032 | Highly Destabilizing | 1.0 | D | 0.824 | deleterious | D | 0.658586355 | None | None | N |
| L/R | 0.988 | likely_pathogenic | 0.9853 | pathogenic | -1.442 | Destabilizing | 1.0 | D | 0.813 | deleterious | D | 0.658586355 | None | None | N |
| L/S | 0.996 | likely_pathogenic | 0.9948 | pathogenic | -2.777 | Highly Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| L/T | 0.9787 | likely_pathogenic | 0.9736 | pathogenic | -2.484 | Highly Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| L/V | 0.5069 | ambiguous | 0.4195 | ambiguous | -1.595 | Destabilizing | 0.999 | D | 0.835 | deleterious | D | 0.590481749 | None | None | N |
| L/W | 0.9859 | likely_pathogenic | 0.9827 | pathogenic | -1.846 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| L/Y | 0.9829 | likely_pathogenic | 0.9797 | pathogenic | -1.619 | Destabilizing | 1.0 | D | 0.795 | 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.