Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9275 | 28048;28049;28050 | chr2:178712007;178712006;178712005 | chr2:179576734;179576733;179576732 |
| N2AB | 8958 | 27097;27098;27099 | chr2:178712007;178712006;178712005 | chr2:179576734;179576733;179576732 |
| N2A | 8031 | 24316;24317;24318 | chr2:178712007;178712006;178712005 | chr2:179576734;179576733;179576732 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs72648996  |
-1.453 | 1.0 | D | 0.889 | 0.921 | 0.883779577115 | gnomAD-2.1.1 | 6.43E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.4055E-04 | 0 |
| Y/C | rs72648996 |
-1.453 | 1.0 | D | 0.889 | 0.921 | 0.883779577115 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 8.82E-05 | 0 | 0 |
| Y/C | rs72648996 |
-1.453 | 1.0 | D | 0.889 | 0.921 | 0.883779577115 |
Taylor (2011)
| None |
ARVC 
|
het | None | None | N | Genetic analysis of TTN in 38 ARVC families, incomplete penetrance | None | None | None | None | None | None | None | None | None | None | None |
| Y/C | rs72648996 |
-1.453 | 1.0 | D | 0.889 | 0.921 | 0.883779577115 | gnomAD-4.0.0 | 4.95845E-05 | None | None | None | None | N | None | 2.66959E-05 | 0 | None | 0 | 0 | None | 1.56211E-05 | 0 | 6.44267E-05 | 0 | 1.60128E-05 |
| Y/S | None | None | 1.0 | D | 0.905 | 0.904 | 0.903802506144 | gnomAD-4.0.0 | 1.36873E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7992E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9958 | likely_pathogenic | 0.998 | pathogenic | -2.283 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| Y/C | 0.9601 | likely_pathogenic | 0.9826 | pathogenic | -1.294 | Destabilizing | 1.0 | D | 0.889 | deleterious | D | 0.662013488 | None | None | N |
| Y/D | 0.9975 | likely_pathogenic | 0.9986 | pathogenic | -2.892 | Highly Destabilizing | 1.0 | D | 0.905 | deleterious | D | 0.662013488 | None | None | N |
| Y/E | 0.9988 | likely_pathogenic | 0.9993 | pathogenic | -2.639 | Highly Destabilizing | 1.0 | D | 0.906 | deleterious | None | None | None | None | N |
| Y/F | 0.2106 | likely_benign | 0.2651 | benign | -0.735 | Destabilizing | 0.999 | D | 0.68 | prob.neutral | D | 0.580161165 | None | None | N |
| Y/G | 0.9931 | likely_pathogenic | 0.9959 | pathogenic | -2.74 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| Y/H | 0.9839 | likely_pathogenic | 0.9907 | pathogenic | -2.011 | Highly Destabilizing | 1.0 | D | 0.799 | deleterious | D | 0.661811684 | None | None | N |
| Y/I | 0.837 | likely_pathogenic | 0.9122 | pathogenic | -0.769 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| Y/K | 0.9988 | likely_pathogenic | 0.9993 | pathogenic | -1.736 | Destabilizing | 1.0 | D | 0.904 | deleterious | None | None | None | None | N |
| Y/L | 0.8584 | likely_pathogenic | 0.894 | pathogenic | -0.769 | Destabilizing | 0.999 | D | 0.79 | deleterious | None | None | None | None | N |
| Y/M | 0.9566 | likely_pathogenic | 0.9761 | pathogenic | -0.727 | Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| Y/N | 0.9824 | likely_pathogenic | 0.9894 | pathogenic | -2.675 | Highly Destabilizing | 1.0 | D | 0.899 | deleterious | D | 0.645994127 | None | None | N |
| Y/P | 0.9993 | likely_pathogenic | 0.9996 | pathogenic | -1.29 | Destabilizing | 1.0 | D | 0.921 | deleterious | None | None | None | None | N |
| Y/Q | 0.9989 | likely_pathogenic | 0.9994 | pathogenic | -2.226 | Highly Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| Y/R | 0.9966 | likely_pathogenic | 0.9978 | pathogenic | -2.013 | Highly Destabilizing | 1.0 | D | 0.902 | deleterious | None | None | None | None | N |
| Y/S | 0.994 | likely_pathogenic | 0.9968 | pathogenic | -2.97 | Highly Destabilizing | 1.0 | D | 0.905 | deleterious | D | 0.662013488 | None | None | N |
| Y/T | 0.9955 | likely_pathogenic | 0.998 | pathogenic | -2.568 | Highly Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| Y/V | 0.8383 | likely_pathogenic | 0.9087 | pathogenic | -1.29 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| Y/W | 0.8847 | likely_pathogenic | 0.9061 | pathogenic | -0.08 | Destabilizing | 1.0 | D | 0.785 | 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.