Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26007 | 78244;78245;78246 | chr2:178568113;178568112;178568111 | chr2:179432840;179432839;179432838 |
| N2AB | 24366 | 73321;73322;73323 | chr2:178568113;178568112;178568111 | chr2:179432840;179432839;179432838 |
| N2A | 23439 | 70540;70541;70542 | chr2:178568113;178568112;178568111 | chr2:179432840;179432839;179432838 |
| N2B | 16942 | 51049;51050;51051 | chr2:178568113;178568112;178568111 | chr2:179432840;179432839;179432838 |
| Novex-1 | 17067 | 51424;51425;51426 | chr2:178568113;178568112;178568111 | chr2:179432840;179432839;179432838 |
| Novex-2 | 17134 | 51625;51626;51627 | chr2:178568113;178568112;178568111 | chr2:179432840;179432839;179432838 |
| 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 | rs786205378  |
None | 0.684 | N | 0.616 | 0.155 | 0.402755899245 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| M/T | rs372188921 |
-1.515 | 0.684 | N | 0.75 | 0.364 | None | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.13E-05 | 0 |
| M/T | rs372188921 |
-1.515 | 0.684 | N | 0.75 | 0.364 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| M/T | rs372188921 |
-1.515 | 0.684 | N | 0.75 | 0.364 | None | gnomAD-4.0.0 | 2.41739E-05 | None | None | None | None | N | None | 1.33547E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.13668E-05 | 0 | 1.60159E-05 |
| M/V | rs777587682 |
-0.582 | 0.309 | N | 0.523 | 0.228 | 0.359763055319 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 8.91E-06 | 0 |
| M/V | rs777587682 |
-0.582 | 0.309 | N | 0.523 | 0.228 | 0.359763055319 | gnomAD-4.0.0 | 1.36869E-06 | None | None | None | None | N | None | 2.98954E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65717E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.6833 | likely_pathogenic | 0.7024 | pathogenic | -1.808 | Destabilizing | 0.004 | N | 0.484 | neutral | None | None | None | None | N |
| M/C | 0.8392 | likely_pathogenic | 0.8484 | pathogenic | -2.091 | Highly Destabilizing | 0.987 | D | 0.773 | deleterious | None | None | None | None | N |
| M/D | 0.998 | likely_pathogenic | 0.9982 | pathogenic | -1.62 | Destabilizing | 0.953 | D | 0.798 | deleterious | None | None | None | None | N |
| M/E | 0.9812 | likely_pathogenic | 0.9836 | pathogenic | -1.358 | Destabilizing | 0.742 | D | 0.765 | deleterious | None | None | None | None | N |
| M/F | 0.7464 | likely_pathogenic | 0.7495 | pathogenic | -0.489 | Destabilizing | 0.953 | D | 0.743 | deleterious | None | None | None | None | N |
| M/G | 0.9627 | likely_pathogenic | 0.9677 | pathogenic | -2.319 | Highly Destabilizing | 0.59 | D | 0.751 | deleterious | None | None | None | None | N |
| M/H | 0.9869 | likely_pathogenic | 0.9872 | pathogenic | -2.188 | Highly Destabilizing | 0.996 | D | 0.764 | deleterious | None | None | None | None | N |
| M/I | 0.4643 | ambiguous | 0.4734 | ambiguous | -0.334 | Destabilizing | 0.684 | D | 0.616 | neutral | N | 0.440055304 | None | None | N |
| M/K | 0.9665 | likely_pathogenic | 0.9705 | pathogenic | -0.874 | Destabilizing | 0.684 | D | 0.767 | deleterious | N | 0.512452367 | None | None | N |
| M/L | 0.3126 | likely_benign | 0.327 | benign | -0.334 | Destabilizing | 0.164 | N | 0.437 | neutral | N | 0.479800197 | None | None | N |
| M/N | 0.981 | likely_pathogenic | 0.982 | pathogenic | -1.354 | Destabilizing | 0.953 | D | 0.794 | deleterious | None | None | None | None | N |
| M/P | 0.9976 | likely_pathogenic | 0.9981 | pathogenic | -0.808 | Destabilizing | 0.953 | D | 0.787 | deleterious | None | None | None | None | N |
| M/Q | 0.9057 | likely_pathogenic | 0.9085 | pathogenic | -0.941 | Destabilizing | 0.953 | D | 0.741 | deleterious | None | None | None | None | N |
| M/R | 0.961 | likely_pathogenic | 0.9653 | pathogenic | -1.286 | Destabilizing | 0.939 | D | 0.829 | deleterious | N | 0.501096061 | None | None | N |
| M/S | 0.8955 | likely_pathogenic | 0.8996 | pathogenic | -1.911 | Destabilizing | 0.59 | D | 0.708 | prob.delet. | None | None | None | None | N |
| M/T | 0.7411 | likely_pathogenic | 0.7561 | pathogenic | -1.499 | Destabilizing | 0.684 | D | 0.75 | deleterious | N | 0.493841133 | None | None | N |
| M/V | 0.1119 | likely_benign | 0.1226 | benign | -0.808 | Destabilizing | 0.309 | N | 0.523 | neutral | N | 0.422949623 | None | None | N |
| M/W | 0.9873 | likely_pathogenic | 0.9894 | pathogenic | -0.827 | Destabilizing | 0.996 | D | 0.751 | deleterious | None | None | None | None | N |
| M/Y | 0.9754 | likely_pathogenic | 0.9776 | pathogenic | -0.739 | Destabilizing | 0.984 | D | 0.813 | 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.