Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21390 | 64393;64394;64395 | chr2:178586733;178586732;178586731 | chr2:179451460;179451459;179451458 |
| N2AB | 19749 | 59470;59471;59472 | chr2:178586733;178586732;178586731 | chr2:179451460;179451459;179451458 |
| N2A | 18822 | 56689;56690;56691 | chr2:178586733;178586732;178586731 | chr2:179451460;179451459;179451458 |
| N2B | 12325 | 37198;37199;37200 | chr2:178586733;178586732;178586731 | chr2:179451460;179451459;179451458 |
| Novex-1 | 12450 | 37573;37574;37575 | chr2:178586733;178586732;178586731 | chr2:179451460;179451459;179451458 |
| Novex-2 | 12517 | 37774;37775;37776 | chr2:178586733;178586732;178586731 | chr2:179451460;179451459;179451458 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | None | None | 1.0 | D | 0.813 | 0.586 | 0.581184446821 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 1.94099E-04 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | rs763262121  |
-0.718 | 1.0 | D | 0.898 | 0.575 | 0.813234845967 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.34E-05 | 0 |
| P/L | rs763262121 |
-0.718 | 1.0 | D | 0.898 | 0.575 | 0.813234845967 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 4.78469E-04 |
| P/L | rs763262121 |
-0.718 | 1.0 | D | 0.898 | 0.575 | 0.813234845967 | gnomAD-4.0.0 | 1.28225E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.15597E-05 | 0 | 2.84738E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.9462 | likely_pathogenic | 0.9118 | pathogenic | -2.087 | Highly Destabilizing | 1.0 | D | 0.813 | deleterious | D | 0.572310441 | None | None | N |
| P/C | 0.9939 | likely_pathogenic | 0.9896 | pathogenic | -1.492 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| P/D | 0.9994 | likely_pathogenic | 0.999 | pathogenic | -2.942 | Highly Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| P/E | 0.9989 | likely_pathogenic | 0.9983 | pathogenic | -2.789 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| P/F | 0.9998 | likely_pathogenic | 0.9997 | pathogenic | -1.354 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| P/G | 0.994 | likely_pathogenic | 0.991 | pathogenic | -2.554 | Highly Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | N |
| P/H | 0.9983 | likely_pathogenic | 0.9975 | pathogenic | -2.409 | Highly Destabilizing | 1.0 | D | 0.86 | deleterious | D | 0.634207322 | None | None | N |
| P/I | 0.9979 | likely_pathogenic | 0.9968 | pathogenic | -0.803 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| P/K | 0.9993 | likely_pathogenic | 0.999 | pathogenic | -1.892 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| P/L | 0.9912 | likely_pathogenic | 0.9874 | pathogenic | -0.803 | Destabilizing | 1.0 | D | 0.898 | deleterious | D | 0.607660188 | None | None | N |
| P/M | 0.9991 | likely_pathogenic | 0.9984 | pathogenic | -0.641 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| P/N | 0.9991 | likely_pathogenic | 0.9985 | pathogenic | -2.056 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| P/Q | 0.9983 | likely_pathogenic | 0.9974 | pathogenic | -2.001 | Highly Destabilizing | 1.0 | D | 0.808 | deleterious | None | None | None | None | N |
| P/R | 0.9964 | likely_pathogenic | 0.9955 | pathogenic | -1.549 | Destabilizing | 1.0 | D | 0.877 | deleterious | D | 0.578286001 | None | None | N |
| P/S | 0.9893 | likely_pathogenic | 0.9804 | pathogenic | -2.555 | Highly Destabilizing | 1.0 | D | 0.826 | deleterious | D | 0.550083355 | None | None | N |
| P/T | 0.9928 | likely_pathogenic | 0.9874 | pathogenic | -2.288 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | D | 0.580405843 | None | None | N |
| P/V | 0.9911 | likely_pathogenic | 0.9869 | pathogenic | -1.204 | Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| P/W | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -1.94 | Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| P/Y | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -1.585 | Destabilizing | 1.0 | D | 0.885 | 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.