Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31883 | 95872;95873;95874 | chr2:178545463;178545462;178545461 | chr2:179410190;179410189;179410188 |
| N2AB | 30242 | 90949;90950;90951 | chr2:178545463;178545462;178545461 | chr2:179410190;179410189;179410188 |
| N2A | 29315 | 88168;88169;88170 | chr2:178545463;178545462;178545461 | chr2:179410190;179410189;179410188 |
| N2B | 22818 | 68677;68678;68679 | chr2:178545463;178545462;178545461 | chr2:179410190;179410189;179410188 |
| Novex-1 | 22943 | 69052;69053;69054 | chr2:178545463;178545462;178545461 | chr2:179410190;179410189;179410188 |
| Novex-2 | 23010 | 69253;69254;69255 | chr2:178545463;178545462;178545461 | chr2:179410190;179410189;179410188 |
| 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/M | rs72648262  |
-1.54 | 1.0 | D | 0.835 | 0.648 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.57E-05 | 0 |
| V/M | rs72648262 |
-1.54 | 1.0 | D | 0.835 | 0.648 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 4.78469E-04 |
| V/M | rs72648262 |
-1.54 | 1.0 | D | 0.835 | 0.648 | None | gnomAD-4.0.0 | 2.43639E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 4.51671E-04 | 3.83511E-05 | 0 | 2.84463E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7964 | likely_pathogenic | 0.7946 | pathogenic | -2.457 | Highly Destabilizing | 0.999 | D | 0.729 | prob.delet. | D | 0.551821105 | None | None | N |
| V/C | 0.9593 | likely_pathogenic | 0.9641 | pathogenic | -2.321 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| V/D | 0.9991 | likely_pathogenic | 0.9991 | pathogenic | -3.495 | Highly Destabilizing | 1.0 | D | 0.919 | deleterious | None | None | None | None | N |
| V/E | 0.9966 | likely_pathogenic | 0.9967 | pathogenic | -3.223 | Highly Destabilizing | 1.0 | D | 0.913 | deleterious | D | 0.648753332 | None | None | N |
| V/F | 0.9605 | likely_pathogenic | 0.9624 | pathogenic | -1.276 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| V/G | 0.9536 | likely_pathogenic | 0.9514 | pathogenic | -3.019 | Highly Destabilizing | 1.0 | D | 0.914 | deleterious | D | 0.648753332 | None | None | N |
| V/H | 0.9993 | likely_pathogenic | 0.9993 | pathogenic | -2.769 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| V/I | 0.1235 | likely_benign | 0.1285 | benign | -0.836 | Destabilizing | 0.998 | D | 0.687 | prob.neutral | None | None | None | None | N |
| V/K | 0.998 | likely_pathogenic | 0.9981 | pathogenic | -2.0 | Highly Destabilizing | 1.0 | D | 0.914 | deleterious | None | None | None | None | N |
| V/L | 0.8234 | likely_pathogenic | 0.8423 | pathogenic | -0.836 | Destabilizing | 0.997 | D | 0.765 | deleterious | D | 0.523571404 | None | None | N |
| V/M | 0.8589 | likely_pathogenic | 0.8718 | pathogenic | -1.238 | Destabilizing | 1.0 | D | 0.835 | deleterious | D | 0.5634309 | None | None | N |
| V/N | 0.9949 | likely_pathogenic | 0.9954 | pathogenic | -2.577 | Highly Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| V/P | 0.9972 | likely_pathogenic | 0.9978 | pathogenic | -1.357 | Destabilizing | 1.0 | D | 0.914 | deleterious | None | None | None | None | N |
| V/Q | 0.9963 | likely_pathogenic | 0.9964 | pathogenic | -2.301 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| V/R | 0.9954 | likely_pathogenic | 0.9954 | pathogenic | -1.939 | Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| V/S | 0.9664 | likely_pathogenic | 0.9661 | pathogenic | -3.115 | Highly Destabilizing | 1.0 | D | 0.906 | deleterious | None | None | None | None | N |
| V/T | 0.9184 | likely_pathogenic | 0.9238 | pathogenic | -2.699 | Highly Destabilizing | 0.999 | D | 0.763 | deleterious | None | None | None | None | N |
| V/W | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -1.86 | Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| V/Y | 0.9965 | likely_pathogenic | 0.997 | pathogenic | -1.596 | Destabilizing | 1.0 | D | 0.881 | 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.