Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18553 | 55882;55883;55884 | chr2:178601340;178601339;178601338 | chr2:179466067;179466066;179466065 |
| N2AB | 16912 | 50959;50960;50961 | chr2:178601340;178601339;178601338 | chr2:179466067;179466066;179466065 |
| N2A | 15985 | 48178;48179;48180 | chr2:178601340;178601339;178601338 | chr2:179466067;179466066;179466065 |
| N2B | 9488 | 28687;28688;28689 | chr2:178601340;178601339;178601338 | chr2:179466067;179466066;179466065 |
| Novex-1 | 9613 | 29062;29063;29064 | chr2:178601340;178601339;178601338 | chr2:179466067;179466066;179466065 |
| Novex-2 | 9680 | 29263;29264;29265 | chr2:178601340;178601339;178601338 | chr2:179466067;179466066;179466065 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs1249794224  |
-1.399 | 0.997 | N | 0.653 | 0.555 | 0.643501137068 | 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 |
| V/L | rs1249794224 |
-1.399 | 0.997 | N | 0.653 | 0.555 | 0.643501137068 | gnomAD-4.0.0 | 6.85663E-07 | None | None | None | None | N | None | 0 | 2.24477E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | None | None | 1.0 | D | 0.78 | 0.594 | 0.677202884781 | gnomAD-4.0.0 | 6.85663E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53447E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.9545 | likely_pathogenic | 0.9379 | pathogenic | -2.883 | Highly Destabilizing | 0.999 | D | 0.639 | neutral | D | 0.551656521 | None | None | N |
| V/C | 0.9769 | likely_pathogenic | 0.9743 | pathogenic | -2.265 | Highly Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| V/D | 0.9992 | likely_pathogenic | 0.999 | pathogenic | -3.654 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| V/E | 0.9964 | likely_pathogenic | 0.9957 | pathogenic | -3.356 | Highly Destabilizing | 1.0 | D | 0.878 | deleterious | D | 0.632501806 | None | None | N |
| V/F | 0.9655 | likely_pathogenic | 0.9414 | pathogenic | -1.707 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| V/G | 0.9662 | likely_pathogenic | 0.9609 | pathogenic | -3.414 | Highly Destabilizing | 1.0 | D | 0.878 | deleterious | D | 0.632501806 | None | None | N |
| V/H | 0.9992 | likely_pathogenic | 0.9989 | pathogenic | -3.05 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| V/I | 0.118 | likely_benign | 0.09 | benign | -1.298 | Destabilizing | 0.998 | D | 0.62 | neutral | None | None | None | None | N |
| V/K | 0.9967 | likely_pathogenic | 0.9963 | pathogenic | -2.499 | Highly Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | N |
| V/L | 0.809 | likely_pathogenic | 0.7082 | pathogenic | -1.298 | Destabilizing | 0.997 | D | 0.653 | neutral | N | 0.519127633 | None | None | N |
| V/M | 0.9108 | likely_pathogenic | 0.8519 | pathogenic | -1.588 | Destabilizing | 1.0 | D | 0.78 | deleterious | D | 0.543516219 | None | None | N |
| V/N | 0.9969 | likely_pathogenic | 0.9963 | pathogenic | -3.18 | Highly Destabilizing | 1.0 | D | 0.9 | deleterious | None | None | None | None | N |
| V/P | 0.9971 | likely_pathogenic | 0.9972 | pathogenic | -1.817 | Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | None | None | N |
| V/Q | 0.996 | likely_pathogenic | 0.9952 | pathogenic | -2.856 | Highly Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| V/R | 0.9938 | likely_pathogenic | 0.9929 | pathogenic | -2.441 | Highly Destabilizing | 1.0 | D | 0.902 | deleterious | None | None | None | None | N |
| V/S | 0.9895 | likely_pathogenic | 0.9862 | pathogenic | -3.619 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| V/T | 0.9689 | likely_pathogenic | 0.9642 | pathogenic | -3.187 | Highly Destabilizing | 0.999 | D | 0.668 | neutral | None | None | None | None | N |
| V/W | 0.9996 | likely_pathogenic | 0.9989 | pathogenic | -2.106 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| V/Y | 0.9969 | likely_pathogenic | 0.9946 | pathogenic | -1.983 | Destabilizing | 1.0 | D | 0.823 | 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.