Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18971 | 57136;57137;57138 | chr2:178598799;178598798;178598797 | chr2:179463526;179463525;179463524 |
| N2AB | 17330 | 52213;52214;52215 | chr2:178598799;178598798;178598797 | chr2:179463526;179463525;179463524 |
| N2A | 16403 | 49432;49433;49434 | chr2:178598799;178598798;178598797 | chr2:179463526;179463525;179463524 |
| N2B | 9906 | 29941;29942;29943 | chr2:178598799;178598798;178598797 | chr2:179463526;179463525;179463524 |
| Novex-1 | 10031 | 30316;30317;30318 | chr2:178598799;178598798;178598797 | chr2:179463526;179463525;179463524 |
| Novex-2 | 10098 | 30517;30518;30519 | chr2:178598799;178598798;178598797 | chr2:179463526;179463525;179463524 |
| 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/M | rs373153121  |
-0.517 | 1.0 | N | 0.701 | 0.148 | None | gnomAD-2.1.1 | 5.72E-05 | None | None | None | None | I | None | 8.27E-05 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 4E-05 | 7.84E-05 | 1.40568E-04 |
| V/M | rs373153121 |
-0.517 | 1.0 | N | 0.701 | 0.148 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | I | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 4.78469E-04 |
| V/M | rs373153121 |
-0.517 | 1.0 | N | 0.701 | 0.148 | None | gnomAD-4.0.0 | 3.71923E-05 | None | None | None | None | I | None | 6.6786E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.89984E-05 | 4.39319E-05 | 8.00794E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2169 | likely_benign | 0.2318 | benign | -1.441 | Destabilizing | 0.91 | D | 0.547 | neutral | N | 0.437014998 | None | None | I |
| V/C | 0.6801 | likely_pathogenic | 0.7079 | pathogenic | -0.976 | Destabilizing | 0.092 | N | 0.427 | neutral | None | None | None | None | I |
| V/D | 0.773 | likely_pathogenic | 0.7851 | pathogenic | -1.076 | Destabilizing | 0.999 | D | 0.829 | deleterious | None | None | None | None | I |
| V/E | 0.5927 | likely_pathogenic | 0.6099 | pathogenic | -1.036 | Destabilizing | 0.998 | D | 0.826 | deleterious | N | 0.46119858 | None | None | I |
| V/F | 0.3511 | ambiguous | 0.3783 | ambiguous | -1.002 | Destabilizing | 0.999 | D | 0.779 | deleterious | None | None | None | None | I |
| V/G | 0.4925 | ambiguous | 0.5113 | ambiguous | -1.793 | Destabilizing | 0.994 | D | 0.797 | deleterious | N | 0.511147398 | None | None | I |
| V/H | 0.8392 | likely_pathogenic | 0.8519 | pathogenic | -1.199 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | I |
| V/I | 0.0735 | likely_benign | 0.0785 | benign | -0.565 | Destabilizing | 0.965 | D | 0.564 | neutral | None | None | None | None | I |
| V/K | 0.7146 | likely_pathogenic | 0.7169 | pathogenic | -1.12 | Destabilizing | 0.999 | D | 0.821 | deleterious | None | None | None | None | I |
| V/L | 0.3106 | likely_benign | 0.3377 | benign | -0.565 | Destabilizing | 0.963 | D | 0.571 | neutral | N | 0.424200417 | None | None | I |
| V/M | 0.2107 | likely_benign | 0.2505 | benign | -0.5 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | N | 0.474879953 | None | None | I |
| V/N | 0.5642 | likely_pathogenic | 0.6079 | pathogenic | -1.014 | Destabilizing | 0.999 | D | 0.827 | deleterious | None | None | None | None | I |
| V/P | 0.402 | ambiguous | 0.4315 | ambiguous | -0.822 | Destabilizing | 0.999 | D | 0.828 | deleterious | None | None | None | None | I |
| V/Q | 0.6018 | likely_pathogenic | 0.6117 | pathogenic | -1.116 | Destabilizing | 0.999 | D | 0.829 | deleterious | None | None | None | None | I |
| V/R | 0.6862 | likely_pathogenic | 0.6622 | pathogenic | -0.641 | Destabilizing | 0.999 | D | 0.829 | deleterious | None | None | None | None | I |
| V/S | 0.383 | ambiguous | 0.4227 | ambiguous | -1.598 | Destabilizing | 0.985 | D | 0.793 | deleterious | None | None | None | None | I |
| V/T | 0.1895 | likely_benign | 0.2112 | benign | -1.433 | Destabilizing | 0.985 | D | 0.595 | neutral | None | None | None | None | I |
| V/W | 0.9193 | likely_pathogenic | 0.9404 | pathogenic | -1.202 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | I |
| V/Y | 0.7801 | likely_pathogenic | 0.7981 | pathogenic | -0.889 | Destabilizing | 0.999 | D | 0.771 | deleterious | None | None | None | None | I |
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.