Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24239 | 72940;72941;72942 | chr2:178573417;178573416;178573415 | chr2:179438144;179438143;179438142 |
| N2AB | 22598 | 68017;68018;68019 | chr2:178573417;178573416;178573415 | chr2:179438144;179438143;179438142 |
| N2A | 21671 | 65236;65237;65238 | chr2:178573417;178573416;178573415 | chr2:179438144;179438143;179438142 |
| N2B | 15174 | 45745;45746;45747 | chr2:178573417;178573416;178573415 | chr2:179438144;179438143;179438142 |
| Novex-1 | 15299 | 46120;46121;46122 | chr2:178573417;178573416;178573415 | chr2:179438144;179438143;179438142 |
| Novex-2 | 15366 | 46321;46322;46323 | chr2:178573417;178573416;178573415 | chr2:179438144;179438143;179438142 |
| 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/K | rs750298083  |
-0.519 | 0.684 | N | 0.778 | 0.514 | None | gnomAD-2.1.1 | 5.31E-05 | None | None | None | None | N | None | 4.31E-05 | 4.66E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-05 | 0 |
| M/K | rs750298083 |
-0.519 | 0.684 | N | 0.778 | 0.514 | None | 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 |
| M/K | rs750298083 |
-0.519 | 0.684 | N | 0.778 | 0.514 | None | gnomAD-4.0.0 | 9.60636E-05 | None | None | None | None | N | None | 1.39431E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.18758E-04 | 0 | 1.71075E-04 |
| M/T | rs750298083 |
-1.14 | 0.684 | N | 0.765 | 0.415 | 0.698338746257 | gnomAD-2.1.1 | 1.93E-05 | None | None | None | None | N | None | 0 | 1.39847E-04 | None | 0 | 0 | None | 0 | None | 0 | 9.86E-06 | 0 |
| M/T | rs750298083 |
-1.14 | 0.684 | N | 0.765 | 0.415 | 0.698338746257 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs750298083 |
-1.14 | 0.684 | N | 0.765 | 0.415 | 0.698338746257 | gnomAD-4.0.0 | 8.55362E-06 | None | None | None | None | N | None | 0 | 8.98998E-05 | None | 0 | 0 | None | 0 | 0 | 3.51875E-06 | 5.43951E-05 | 1.71075E-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 | 0.7008 | likely_pathogenic | 0.6419 | pathogenic | -1.926 | Destabilizing | 0.004 | N | 0.491 | neutral | None | None | None | None | N |
| M/C | 0.8741 | likely_pathogenic | 0.8499 | pathogenic | -2.289 | Highly Destabilizing | 0.987 | D | 0.792 | deleterious | None | None | None | None | N |
| M/D | 0.9992 | likely_pathogenic | 0.9987 | pathogenic | -2.041 | Highly Destabilizing | 0.953 | D | 0.818 | deleterious | None | None | None | None | N |
| M/E | 0.9925 | likely_pathogenic | 0.9892 | pathogenic | -1.765 | Destabilizing | 0.742 | D | 0.773 | deleterious | None | None | None | None | N |
| M/F | 0.8769 | likely_pathogenic | 0.8376 | pathogenic | -0.446 | Destabilizing | 0.953 | D | 0.715 | prob.delet. | None | None | None | None | N |
| M/G | 0.9785 | likely_pathogenic | 0.9669 | pathogenic | -2.432 | Highly Destabilizing | 0.59 | D | 0.753 | deleterious | None | None | None | None | N |
| M/H | 0.9961 | likely_pathogenic | 0.993 | pathogenic | -2.298 | Highly Destabilizing | 0.996 | D | 0.781 | deleterious | None | None | None | None | N |
| M/I | 0.7638 | likely_pathogenic | 0.6923 | pathogenic | -0.453 | Destabilizing | 0.684 | D | 0.586 | neutral | N | 0.454600682 | None | None | N |
| M/K | 0.9874 | likely_pathogenic | 0.9795 | pathogenic | -1.143 | Destabilizing | 0.684 | D | 0.778 | deleterious | N | 0.517719059 | None | None | N |
| M/L | 0.4598 | ambiguous | 0.376 | ambiguous | -0.453 | Destabilizing | 0.164 | N | 0.412 | neutral | N | 0.483032503 | None | None | N |
| M/N | 0.9944 | likely_pathogenic | 0.9893 | pathogenic | -1.676 | Destabilizing | 0.953 | D | 0.817 | deleterious | None | None | None | None | N |
| M/P | 0.9994 | likely_pathogenic | 0.9989 | pathogenic | -0.929 | Destabilizing | 0.953 | D | 0.805 | deleterious | None | None | None | None | N |
| M/Q | 0.9585 | likely_pathogenic | 0.94 | pathogenic | -1.237 | Destabilizing | 0.953 | D | 0.715 | prob.delet. | None | None | None | None | N |
| M/R | 0.9847 | likely_pathogenic | 0.9747 | pathogenic | -1.546 | Destabilizing | 0.939 | D | 0.829 | deleterious | N | 0.517719059 | None | None | N |
| M/S | 0.9363 | likely_pathogenic | 0.9042 | pathogenic | -2.153 | Highly Destabilizing | 0.59 | D | 0.712 | prob.delet. | None | None | None | None | N |
| M/T | 0.8896 | likely_pathogenic | 0.8241 | pathogenic | -1.737 | Destabilizing | 0.684 | D | 0.765 | deleterious | N | 0.494334885 | None | None | N |
| M/V | 0.2165 | likely_benign | 0.1868 | benign | -0.929 | Destabilizing | 0.309 | N | 0.503 | neutral | N | 0.410828475 | None | None | N |
| M/W | 0.9964 | likely_pathogenic | 0.9935 | pathogenic | -0.829 | Destabilizing | 0.996 | D | 0.759 | deleterious | None | None | None | None | N |
| M/Y | 0.9918 | likely_pathogenic | 0.9871 | pathogenic | -0.773 | Destabilizing | 0.984 | D | 0.832 | 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.