Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23301 | 70126;70127;70128 | chr2:178576231;178576230;178576229 | chr2:179440958;179440957;179440956 |
| N2AB | 21660 | 65203;65204;65205 | chr2:178576231;178576230;178576229 | chr2:179440958;179440957;179440956 |
| N2A | 20733 | 62422;62423;62424 | chr2:178576231;178576230;178576229 | chr2:179440958;179440957;179440956 |
| N2B | 14236 | 42931;42932;42933 | chr2:178576231;178576230;178576229 | chr2:179440958;179440957;179440956 |
| Novex-1 | 14361 | 43306;43307;43308 | chr2:178576231;178576230;178576229 | chr2:179440958;179440957;179440956 |
| Novex-2 | 14428 | 43507;43508;43509 | chr2:178576231;178576230;178576229 | chr2:179440958;179440957;179440956 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs372799151  |
-1.189 | 0.805 | N | 0.531 | 0.339 | 0.466740653422 | gnomAD-2.1.1 | 2.26111E-04 | None | None | None | None | I | None | 2.60675E-03 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| F/L | rs372799151 |
-1.189 | 0.805 | N | 0.531 | 0.339 | 0.466740653422 | gnomAD-3.1.2 | 7.43147E-04 | None | None | None | None | I | None | 2.65534E-03 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 9.56938E-04 |
| F/L | rs372799151 |
-1.189 | 0.805 | N | 0.531 | 0.339 | 0.466740653422 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| F/L | rs372799151 |
-1.189 | 0.805 | N | 0.531 | 0.339 | 0.466740653422 | gnomAD-4.0.0 | 1.22144E-04 | None | None | None | None | I | None | 2.5078E-03 | 3.33745E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.12079E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.94 | likely_pathogenic | 0.9078 | pathogenic | -2.229 | Highly Destabilizing | 0.916 | D | 0.525 | neutral | None | None | None | None | I |
| F/C | 0.7191 | likely_pathogenic | 0.6104 | pathogenic | -1.646 | Destabilizing | 0.999 | D | 0.696 | prob.neutral | N | 0.48777468 | None | None | I |
| F/D | 0.9844 | likely_pathogenic | 0.9798 | pathogenic | -2.008 | Highly Destabilizing | 0.996 | D | 0.749 | deleterious | None | None | None | None | I |
| F/E | 0.9847 | likely_pathogenic | 0.9805 | pathogenic | -1.83 | Destabilizing | 0.987 | D | 0.716 | prob.delet. | None | None | None | None | I |
| F/G | 0.9705 | likely_pathogenic | 0.9565 | pathogenic | -2.625 | Highly Destabilizing | 0.987 | D | 0.655 | neutral | None | None | None | None | I |
| F/H | 0.8443 | likely_pathogenic | 0.8009 | pathogenic | -0.975 | Destabilizing | 0.975 | D | 0.613 | neutral | None | None | None | None | I |
| F/I | 0.765 | likely_pathogenic | 0.6926 | pathogenic | -0.979 | Destabilizing | 0.967 | D | 0.469 | neutral | N | 0.512670337 | None | None | I |
| F/K | 0.9796 | likely_pathogenic | 0.9729 | pathogenic | -1.941 | Destabilizing | 0.987 | D | 0.72 | prob.delet. | None | None | None | None | I |
| F/L | 0.9716 | likely_pathogenic | 0.9566 | pathogenic | -0.979 | Destabilizing | 0.805 | D | 0.531 | neutral | N | 0.482731432 | None | None | I |
| F/M | 0.839 | likely_pathogenic | 0.7938 | pathogenic | -0.826 | Destabilizing | 0.999 | D | 0.521 | neutral | None | None | None | None | I |
| F/N | 0.9563 | likely_pathogenic | 0.9418 | pathogenic | -2.389 | Highly Destabilizing | 0.987 | D | 0.765 | deleterious | None | None | None | None | I |
| F/P | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -1.399 | Destabilizing | 0.996 | D | 0.77 | deleterious | None | None | None | None | I |
| F/Q | 0.9668 | likely_pathogenic | 0.9561 | pathogenic | -2.29 | Highly Destabilizing | 0.987 | D | 0.771 | deleterious | None | None | None | None | I |
| F/R | 0.9533 | likely_pathogenic | 0.9392 | pathogenic | -1.485 | Destabilizing | 0.987 | D | 0.765 | deleterious | None | None | None | None | I |
| F/S | 0.9322 | likely_pathogenic | 0.9015 | pathogenic | -3.061 | Highly Destabilizing | 0.983 | D | 0.607 | neutral | N | 0.474877958 | None | None | I |
| F/T | 0.9486 | likely_pathogenic | 0.9252 | pathogenic | -2.773 | Highly Destabilizing | 0.987 | D | 0.633 | neutral | None | None | None | None | I |
| F/V | 0.7422 | likely_pathogenic | 0.6698 | pathogenic | -1.399 | Destabilizing | 0.892 | D | 0.472 | neutral | N | 0.495388511 | None | None | I |
| F/W | 0.6206 | likely_pathogenic | 0.5857 | pathogenic | -0.067 | Destabilizing | 0.997 | D | 0.507 | neutral | None | None | None | None | I |
| F/Y | 0.1465 | likely_benign | 0.1293 | benign | -0.405 | Destabilizing | 0.011 | N | 0.254 | neutral | N | 0.418871955 | 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.