Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31036 | 93331;93332;93333 | chr2:178548520;178548519;178548518 | chr2:179413247;179413246;179413245 |
| N2AB | 29395 | 88408;88409;88410 | chr2:178548520;178548519;178548518 | chr2:179413247;179413246;179413245 |
| N2A | 28468 | 85627;85628;85629 | chr2:178548520;178548519;178548518 | chr2:179413247;179413246;179413245 |
| N2B | 21971 | 66136;66137;66138 | chr2:178548520;178548519;178548518 | chr2:179413247;179413246;179413245 |
| Novex-1 | 22096 | 66511;66512;66513 | chr2:178548520;178548519;178548518 | chr2:179413247;179413246;179413245 |
| Novex-2 | 22163 | 66712;66713;66714 | chr2:178548520;178548519;178548518 | chr2:179413247;179413246;179413245 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/T | rs376942948  |
-1.556 | 0.007 | N | 0.307 | 0.278 | None | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.66963E-04 | None | 6.54E-05 | None | 0 | 1.78E-05 | 0 |
| M/T | rs376942948 |
-1.556 | 0.007 | N | 0.307 | 0.278 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.85654E-04 | None | 0 | 0 | 4.41E-05 | 2.07383E-04 | 0 |
| M/T | rs376942948 |
-1.556 | 0.007 | N | 0.307 | 0.278 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 1E-03 | None |
| M/T | rs376942948 |
-1.556 | 0.007 | N | 0.307 | 0.278 | None | gnomAD-4.0.0 | 2.16874E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.55999E-04 | None | 0 | 0 | 9.32368E-06 | 6.5879E-05 | 1.76039E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5878 | likely_pathogenic | 0.4531 | ambiguous | -2.171 | Highly Destabilizing | 0.228 | N | 0.418 | neutral | None | None | None | None | N |
| M/C | 0.7558 | likely_pathogenic | 0.6994 | pathogenic | -1.592 | Destabilizing | 0.983 | D | 0.542 | neutral | None | None | None | None | N |
| M/D | 0.9782 | likely_pathogenic | 0.9498 | pathogenic | -1.115 | Destabilizing | 0.836 | D | 0.569 | neutral | None | None | None | None | N |
| M/E | 0.8523 | likely_pathogenic | 0.7243 | pathogenic | -0.98 | Destabilizing | 0.593 | D | 0.516 | neutral | None | None | None | None | N |
| M/F | 0.4896 | ambiguous | 0.4103 | ambiguous | -0.766 | Destabilizing | 0.557 | D | 0.462 | neutral | None | None | None | None | N |
| M/G | 0.8105 | likely_pathogenic | 0.6901 | pathogenic | -2.584 | Highly Destabilizing | 0.593 | D | 0.469 | neutral | None | None | None | None | N |
| M/H | 0.7176 | likely_pathogenic | 0.5895 | pathogenic | -1.769 | Destabilizing | 0.983 | D | 0.532 | neutral | None | None | None | None | N |
| M/I | 0.5367 | ambiguous | 0.449 | ambiguous | -1.031 | Destabilizing | 0.101 | N | 0.354 | neutral | N | 0.422549765 | None | None | N |
| M/K | 0.5942 | likely_pathogenic | 0.4167 | ambiguous | -1.097 | Destabilizing | 0.523 | D | 0.414 | neutral | N | 0.397824679 | None | None | N |
| M/L | 0.1228 | likely_benign | 0.1176 | benign | -1.031 | Destabilizing | None | N | 0.179 | neutral | N | 0.378585557 | None | None | N |
| M/N | 0.7519 | likely_pathogenic | 0.6195 | pathogenic | -1.156 | Destabilizing | 0.836 | D | 0.585 | neutral | None | None | None | None | N |
| M/P | 0.989 | likely_pathogenic | 0.9755 | pathogenic | -1.388 | Destabilizing | 0.002 | N | 0.453 | neutral | None | None | None | None | N |
| M/Q | 0.4326 | ambiguous | 0.3069 | benign | -1.05 | Destabilizing | 0.94 | D | 0.478 | neutral | None | None | None | None | N |
| M/R | 0.5939 | likely_pathogenic | 0.4234 | ambiguous | -0.811 | Destabilizing | 0.794 | D | 0.561 | neutral | N | 0.395515093 | None | None | N |
| M/S | 0.5274 | ambiguous | 0.3981 | ambiguous | -1.818 | Destabilizing | 0.264 | N | 0.381 | neutral | None | None | None | None | N |
| M/T | 0.3152 | likely_benign | 0.2385 | benign | -1.564 | Destabilizing | 0.007 | N | 0.307 | neutral | N | 0.305837238 | None | None | N |
| M/V | 0.1742 | likely_benign | 0.1472 | benign | -1.388 | Destabilizing | 0.101 | N | 0.359 | neutral | N | 0.37712412 | None | None | N |
| M/W | 0.8155 | likely_pathogenic | 0.7489 | pathogenic | -0.855 | Destabilizing | 0.983 | D | 0.543 | neutral | None | None | None | None | N |
| M/Y | 0.7655 | likely_pathogenic | 0.6653 | pathogenic | -0.904 | Destabilizing | 0.836 | D | 0.552 | 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.