Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23818 | 71677;71678;71679 | chr2:178574680;178574679;178574678 | chr2:179439407;179439406;179439405 |
| N2AB | 22177 | 66754;66755;66756 | chr2:178574680;178574679;178574678 | chr2:179439407;179439406;179439405 |
| N2A | 21250 | 63973;63974;63975 | chr2:178574680;178574679;178574678 | chr2:179439407;179439406;179439405 |
| N2B | 14753 | 44482;44483;44484 | chr2:178574680;178574679;178574678 | chr2:179439407;179439406;179439405 |
| Novex-1 | 14878 | 44857;44858;44859 | chr2:178574680;178574679;178574678 | chr2:179439407;179439406;179439405 |
| Novex-2 | 14945 | 45058;45059;45060 | chr2:178574680;178574679;178574678 | chr2:179439407;179439406;179439405 |
| 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/T | rs749803403  |
-2.051 | 0.03 | N | 0.546 | 0.246 | 0.635304889077 | gnomAD-2.1.1 | 7.16E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 9.7918E-04 | None | 3.28E-05 | None | 0 | 0 | 0 |
| I/T | rs749803403 |
-2.051 | 0.03 | N | 0.546 | 0.246 | 0.635304889077 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.35712E-03 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs749803403 |
-2.051 | 0.03 | N | 0.546 | 0.246 | 0.635304889077 | gnomAD-4.0.0 | 3.65736E-05 | None | None | None | None | N | None | 0 | 1.66817E-05 | None | 0 | 1.25061E-03 | None | 0 | 0 | 8.47775E-07 | 1.09885E-05 | 0 |
| I/V | rs776911847 |
-0.852 | None | N | 0.111 | 0.056 | 0.110078149338 | gnomAD-2.1.1 | 8.23E-05 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 0 | None | 6.55E-05 | None | 4.01E-05 | 1.48723E-04 | 0 |
| I/V | rs776911847 |
-0.852 | None | N | 0.111 | 0.056 | 0.110078149338 | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.6176E-04 | 0 | 0 |
| I/V | rs776911847 |
-0.852 | None | N | 0.111 | 0.056 | 0.110078149338 | gnomAD-4.0.0 | 3.5331E-05 | None | None | None | None | N | None | 1.33291E-05 | 1.66728E-05 | None | 0 | 0 | None | 3.12529E-05 | 1.65289E-04 | 4.0693E-05 | 2.198E-05 | 3.20215E-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 | 0.2974 | likely_benign | 0.2111 | benign | -2.208 | Highly Destabilizing | 0.016 | N | 0.446 | neutral | None | None | None | None | N |
| I/C | 0.6425 | likely_pathogenic | 0.5165 | ambiguous | -1.489 | Destabilizing | 0.685 | D | 0.565 | neutral | None | None | None | None | N |
| I/D | 0.9098 | likely_pathogenic | 0.8251 | pathogenic | -2.165 | Highly Destabilizing | 0.366 | N | 0.717 | prob.delet. | None | None | None | None | N |
| I/E | 0.7521 | likely_pathogenic | 0.6315 | pathogenic | -1.967 | Destabilizing | 0.366 | N | 0.685 | prob.delet. | None | None | None | None | N |
| I/F | 0.2361 | likely_benign | 0.192 | benign | -1.296 | Destabilizing | 0.221 | N | 0.539 | neutral | None | None | None | None | N |
| I/G | 0.7618 | likely_pathogenic | 0.6227 | pathogenic | -2.699 | Highly Destabilizing | 0.141 | N | 0.637 | neutral | None | None | None | None | N |
| I/H | 0.7115 | likely_pathogenic | 0.5738 | pathogenic | -1.823 | Destabilizing | 0.869 | D | 0.72 | deleterious | None | None | None | None | N |
| I/K | 0.5867 | likely_pathogenic | 0.4643 | ambiguous | -1.7 | Destabilizing | 0.303 | N | 0.689 | prob.delet. | N | 0.500118102 | None | None | N |
| I/L | 0.1263 | likely_benign | 0.1171 | benign | -0.814 | Destabilizing | 0.002 | N | 0.332 | neutral | N | 0.502853201 | None | None | N |
| I/M | 0.1091 | likely_benign | 0.0922 | benign | -0.738 | Destabilizing | 0.177 | N | 0.562 | neutral | N | 0.521249748 | None | None | N |
| I/N | 0.6025 | likely_pathogenic | 0.4637 | ambiguous | -2.017 | Highly Destabilizing | 0.637 | D | 0.747 | deleterious | None | None | None | None | N |
| I/P | 0.9301 | likely_pathogenic | 0.8764 | pathogenic | -1.257 | Destabilizing | 0.637 | D | 0.724 | deleterious | None | None | None | None | N |
| I/Q | 0.6209 | likely_pathogenic | 0.4783 | ambiguous | -1.919 | Destabilizing | 0.637 | D | 0.757 | deleterious | None | None | None | None | N |
| I/R | 0.4957 | ambiguous | 0.3665 | ambiguous | -1.356 | Destabilizing | 0.303 | N | 0.749 | deleterious | N | 0.500118102 | None | None | N |
| I/S | 0.4255 | ambiguous | 0.3163 | benign | -2.708 | Highly Destabilizing | 0.075 | N | 0.531 | neutral | None | None | None | None | N |
| I/T | 0.1808 | likely_benign | 0.1219 | benign | -2.357 | Highly Destabilizing | 0.03 | N | 0.546 | neutral | N | 0.475631064 | None | None | N |
| I/V | 0.0557 | likely_benign | 0.0489 | benign | -1.257 | Destabilizing | None | N | 0.111 | neutral | N | 0.385911388 | None | None | N |
| I/W | 0.9206 | likely_pathogenic | 0.8452 | pathogenic | -1.53 | Destabilizing | 0.869 | D | 0.756 | deleterious | None | None | None | None | N |
| I/Y | 0.698 | likely_pathogenic | 0.6229 | pathogenic | -1.245 | Destabilizing | 0.366 | N | 0.596 | neutral | 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.