Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18901 | 56926;56927;56928 | chr2:178599009;178599008;178599007 | chr2:179463736;179463735;179463734 |
| N2AB | 17260 | 52003;52004;52005 | chr2:178599009;178599008;178599007 | chr2:179463736;179463735;179463734 |
| N2A | 16333 | 49222;49223;49224 | chr2:178599009;178599008;178599007 | chr2:179463736;179463735;179463734 |
| N2B | 9836 | 29731;29732;29733 | chr2:178599009;178599008;178599007 | chr2:179463736;179463735;179463734 |
| Novex-1 | 9961 | 30106;30107;30108 | chr2:178599009;178599008;178599007 | chr2:179463736;179463735;179463734 |
| Novex-2 | 10028 | 30307;30308;30309 | chr2:178599009;178599008;178599007 | chr2:179463736;179463735;179463734 |
| 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/I | rs761136728  |
-0.182 | 0.828 | N | 0.614 | 0.229 | 0.445410361449 | gnomAD-2.1.1 | 4.13E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.16E-06 | 0 |
| M/I | rs761136728 |
-0.182 | 0.828 | N | 0.614 | 0.229 | 0.445410361449 | gnomAD-4.0.0 | 3.21836E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.77811E-06 | 0 | 0 |
| M/L | None | None | 0.03 | N | 0.232 | 0.181 | 0.304435445954 | gnomAD-4.0.0 | 1.60873E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.44907E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.8627 | likely_pathogenic | 0.8014 | pathogenic | -1.897 | Destabilizing | 0.963 | D | 0.675 | prob.neutral | None | None | None | None | N |
| M/C | 0.8974 | likely_pathogenic | 0.8533 | pathogenic | -2.643 | Highly Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| M/D | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -1.977 | Destabilizing | 0.999 | D | 0.809 | deleterious | None | None | None | None | N |
| M/E | 0.9967 | likely_pathogenic | 0.9953 | pathogenic | -1.759 | Destabilizing | 0.999 | D | 0.787 | deleterious | None | None | None | None | N |
| M/F | 0.8889 | likely_pathogenic | 0.8763 | pathogenic | -0.665 | Destabilizing | 0.969 | D | 0.697 | prob.neutral | None | None | None | None | N |
| M/G | 0.9919 | likely_pathogenic | 0.9883 | pathogenic | -2.359 | Highly Destabilizing | 0.999 | D | 0.771 | deleterious | None | None | None | None | N |
| M/H | 0.9981 | likely_pathogenic | 0.9974 | pathogenic | -2.091 | Highly Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| M/I | 0.7511 | likely_pathogenic | 0.7825 | pathogenic | -0.586 | Destabilizing | 0.828 | D | 0.614 | neutral | N | 0.433321332 | None | None | N |
| M/K | 0.992 | likely_pathogenic | 0.9876 | pathogenic | -1.14 | Destabilizing | 0.993 | D | 0.776 | deleterious | N | 0.504716912 | None | None | N |
| M/L | 0.5554 | ambiguous | 0.5508 | ambiguous | -0.586 | Destabilizing | 0.03 | N | 0.232 | neutral | N | 0.456365976 | None | None | N |
| M/N | 0.997 | likely_pathogenic | 0.996 | pathogenic | -1.546 | Destabilizing | 0.999 | D | 0.797 | deleterious | None | None | None | None | N |
| M/P | 0.9998 | likely_pathogenic | 0.9997 | pathogenic | -1.003 | Destabilizing | 0.999 | D | 0.797 | deleterious | None | None | None | None | N |
| M/Q | 0.9689 | likely_pathogenic | 0.9551 | pathogenic | -1.261 | Destabilizing | 0.999 | D | 0.716 | prob.delet. | None | None | None | None | N |
| M/R | 0.9925 | likely_pathogenic | 0.9891 | pathogenic | -1.328 | Destabilizing | 0.998 | D | 0.807 | deleterious | N | 0.493196023 | None | None | N |
| M/S | 0.975 | likely_pathogenic | 0.9648 | pathogenic | -2.102 | Highly Destabilizing | 0.995 | D | 0.768 | deleterious | None | None | None | None | N |
| M/T | 0.9665 | likely_pathogenic | 0.9569 | pathogenic | -1.747 | Destabilizing | 0.979 | D | 0.757 | deleterious | N | 0.486105678 | None | None | N |
| M/V | 0.2599 | likely_benign | 0.2563 | benign | -1.003 | Destabilizing | 0.828 | D | 0.483 | neutral | N | 0.416485011 | None | None | N |
| M/W | 0.9978 | likely_pathogenic | 0.9973 | pathogenic | -0.984 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| M/Y | 0.9946 | likely_pathogenic | 0.9929 | pathogenic | -0.876 | Destabilizing | 0.999 | D | 0.809 | 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.