Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32142 | 96649;96650;96651 | chr2:178543549;178543548;178543547 | chr2:179408276;179408275;179408274 |
| N2AB | 30501 | 91726;91727;91728 | chr2:178543549;178543548;178543547 | chr2:179408276;179408275;179408274 |
| N2A | 29574 | 88945;88946;88947 | chr2:178543549;178543548;178543547 | chr2:179408276;179408275;179408274 |
| N2B | 23077 | 69454;69455;69456 | chr2:178543549;178543548;178543547 | chr2:179408276;179408275;179408274 |
| Novex-1 | 23202 | 69829;69830;69831 | chr2:178543549;178543548;178543547 | chr2:179408276;179408275;179408274 |
| Novex-2 | 23269 | 70030;70031;70032 | chr2:178543549;178543548;178543547 | chr2:179408276;179408275;179408274 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1695611620  |
None | 0.184 | D | 0.47 | 0.554 | 0.655853083524 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07383E-04 | 0 |
| V/A | rs1695611620 |
None | 0.184 | D | 0.47 | 0.554 | 0.655853083524 | gnomAD-4.0.0 | 1.8609E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47654E-07 | 1.09818E-05 | 1.6019E-05 |
| V/I | rs779663332 |
-0.714 | 0.001 | N | 0.185 | 0.068 | None | gnomAD-2.1.1 | 8.1E-05 | None | None | None | None | N | None | 0 | 8.71E-05 | None | 0 | 0 | None | 0 | None | 2.93485E-04 | 8.03E-05 | 3.33667E-04 |
| V/I | rs779663332 |
-0.714 | 0.001 | N | 0.185 | 0.068 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 1.88537E-04 | 0 | 7.35E-05 | 0 | 0 |
| V/I | rs779663332 |
-0.714 | 0.001 | N | 0.185 | 0.068 | None | gnomAD-4.0.0 | 9.05727E-05 | None | None | None | None | N | None | 4.00523E-05 | 3.33489E-05 | None | 0 | 2.23035E-05 | None | 3.36247E-04 | 0 | 8.81559E-05 | 1.09818E-05 | 2.24266E-04 |
| V/L | None | None | 0.003 | N | 0.361 | 0.096 | 0.272205846399 | gnomAD-4.0.0 | 6.85027E-07 | None | None | None | None | N | None | 0 | 2.23704E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.8053 | likely_pathogenic | 0.7436 | pathogenic | -2.539 | Highly Destabilizing | 0.184 | N | 0.47 | neutral | D | 0.528968865 | None | None | N |
| V/C | 0.9543 | likely_pathogenic | 0.9378 | pathogenic | -1.858 | Destabilizing | 0.94 | D | 0.775 | deleterious | None | None | None | None | N |
| V/D | 0.998 | likely_pathogenic | 0.9968 | pathogenic | -3.387 | Highly Destabilizing | 0.997 | D | 0.794 | deleterious | D | 0.541250224 | None | None | N |
| V/E | 0.9919 | likely_pathogenic | 0.9871 | pathogenic | -3.052 | Highly Destabilizing | 0.984 | D | 0.757 | deleterious | None | None | None | None | N |
| V/F | 0.7881 | likely_pathogenic | 0.6994 | pathogenic | -1.371 | Destabilizing | 0.72 | D | 0.62 | neutral | D | 0.540996734 | None | None | N |
| V/G | 0.9619 | likely_pathogenic | 0.9355 | pathogenic | -3.156 | Highly Destabilizing | 0.787 | D | 0.771 | deleterious | D | 0.541250224 | None | None | N |
| V/H | 0.9968 | likely_pathogenic | 0.9947 | pathogenic | -3.007 | Highly Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| V/I | 0.0574 | likely_benign | 0.0601 | benign | -0.72 | Destabilizing | 0.001 | N | 0.185 | neutral | N | 0.459110785 | None | None | N |
| V/K | 0.9916 | likely_pathogenic | 0.9871 | pathogenic | -1.931 | Destabilizing | 0.993 | D | 0.757 | deleterious | None | None | None | None | N |
| V/L | 0.2992 | likely_benign | 0.2333 | benign | -0.72 | Destabilizing | 0.003 | N | 0.361 | neutral | N | 0.520375462 | None | None | N |
| V/M | 0.5194 | ambiguous | 0.4287 | ambiguous | -1.056 | Destabilizing | 0.771 | D | 0.572 | neutral | None | None | None | None | N |
| V/N | 0.9921 | likely_pathogenic | 0.9882 | pathogenic | -2.67 | Highly Destabilizing | 0.984 | D | 0.84 | deleterious | None | None | None | None | N |
| V/P | 0.9763 | likely_pathogenic | 0.9668 | pathogenic | -1.312 | Destabilizing | 0.984 | D | 0.804 | deleterious | None | None | None | None | N |
| V/Q | 0.9906 | likely_pathogenic | 0.9842 | pathogenic | -2.266 | Highly Destabilizing | 0.997 | D | 0.827 | deleterious | None | None | None | None | N |
| V/R | 0.9835 | likely_pathogenic | 0.9748 | pathogenic | -2.107 | Highly Destabilizing | 0.997 | D | 0.841 | deleterious | None | None | None | None | N |
| V/S | 0.9628 | likely_pathogenic | 0.943 | pathogenic | -3.153 | Highly Destabilizing | 0.978 | D | 0.715 | prob.delet. | None | None | None | None | N |
| V/T | 0.793 | likely_pathogenic | 0.7383 | pathogenic | -2.655 | Highly Destabilizing | 0.9 | D | 0.539 | neutral | None | None | None | None | N |
| V/W | 0.9947 | likely_pathogenic | 0.9893 | pathogenic | -1.882 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| V/Y | 0.9848 | likely_pathogenic | 0.9744 | pathogenic | -1.647 | Destabilizing | 0.997 | D | 0.7 | prob.neutral | 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.