Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22334 | 67225;67226;67227 | chr2:178580379;178580378;178580377 | chr2:179445106;179445105;179445104 |
| N2AB | 20693 | 62302;62303;62304 | chr2:178580379;178580378;178580377 | chr2:179445106;179445105;179445104 |
| N2A | 19766 | 59521;59522;59523 | chr2:178580379;178580378;178580377 | chr2:179445106;179445105;179445104 |
| N2B | 13269 | 40030;40031;40032 | chr2:178580379;178580378;178580377 | chr2:179445106;179445105;179445104 |
| Novex-1 | 13394 | 40405;40406;40407 | chr2:178580379;178580378;178580377 | chr2:179445106;179445105;179445104 |
| Novex-2 | 13461 | 40606;40607;40608 | chr2:178580379;178580378;178580377 | chr2:179445106;179445105;179445104 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/S | rs758106978  |
-3.128 | 1.0 | N | 0.888 | 0.539 | 0.761447629884 | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.59823E-04 | None | 0 | None | 0 | 0 | 0 |
| L/S | rs758106978 |
-3.128 | 1.0 | N | 0.888 | 0.539 | 0.761447629884 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93723E-04 | None | 0 | 0 | 0 | 0 | 0 |
| L/S | rs758106978 |
-3.128 | 1.0 | N | 0.888 | 0.539 | 0.761447629884 | gnomAD-4.0.0 | 3.71944E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.33887E-04 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | rs766103894 |
-1.142 | 0.999 | N | 0.773 | 0.247 | 0.308904156042 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| L/V | rs766103894 |
-1.142 | 0.999 | N | 0.773 | 0.247 | 0.308904156042 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/V | rs766103894 |
-1.142 | 0.999 | N | 0.773 | 0.247 | 0.308904156042 | gnomAD-4.0.0 | 4.3393E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.93494E-06 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9439 | likely_pathogenic | 0.9443 | pathogenic | -2.291 | Highly Destabilizing | 0.999 | D | 0.835 | deleterious | None | None | None | None | N |
| L/C | 0.8851 | likely_pathogenic | 0.8825 | pathogenic | -1.61 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| L/D | 0.9997 | likely_pathogenic | 0.9998 | pathogenic | -2.536 | Highly Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| L/E | 0.9979 | likely_pathogenic | 0.9981 | pathogenic | -2.247 | Highly Destabilizing | 1.0 | D | 0.89 | deleterious | None | None | None | None | N |
| L/F | 0.7947 | likely_pathogenic | 0.7654 | pathogenic | -1.324 | Destabilizing | 1.0 | D | 0.881 | deleterious | N | 0.452742826 | None | None | N |
| L/G | 0.9933 | likely_pathogenic | 0.9931 | pathogenic | -2.897 | Highly Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | N |
| L/H | 0.9948 | likely_pathogenic | 0.9947 | pathogenic | -2.481 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| L/I | 0.1835 | likely_benign | 0.1853 | benign | -0.519 | Destabilizing | 0.999 | D | 0.745 | deleterious | N | 0.453437528 | None | None | N |
| L/K | 0.996 | likely_pathogenic | 0.9966 | pathogenic | -1.658 | Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| L/M | 0.3583 | ambiguous | 0.3547 | ambiguous | -0.601 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| L/N | 0.9977 | likely_pathogenic | 0.9979 | pathogenic | -2.178 | Highly Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| L/P | 0.9974 | likely_pathogenic | 0.9974 | pathogenic | -1.093 | Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| L/Q | 0.989 | likely_pathogenic | 0.9891 | pathogenic | -1.898 | Destabilizing | 1.0 | D | 0.904 | deleterious | None | None | None | None | N |
| L/R | 0.9919 | likely_pathogenic | 0.9923 | pathogenic | -1.646 | Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| L/S | 0.9949 | likely_pathogenic | 0.9949 | pathogenic | -2.895 | Highly Destabilizing | 1.0 | D | 0.888 | deleterious | N | 0.483724324 | None | None | N |
| L/T | 0.9764 | likely_pathogenic | 0.9771 | pathogenic | -2.433 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| L/V | 0.2155 | likely_benign | 0.2167 | benign | -1.093 | Destabilizing | 0.999 | D | 0.773 | deleterious | N | 0.437121281 | None | None | N |
| L/W | 0.9889 | likely_pathogenic | 0.987 | pathogenic | -1.72 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| L/Y | 0.9865 | likely_pathogenic | 0.9848 | pathogenic | -1.385 | Destabilizing | 1.0 | D | 0.878 | 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.