TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16785	50578;50579;50580	chr2:178612058;178612057;178611954	chr2:179476785;179476784;179476681
N2AB	15144	45655;45656;45657	chr2:178612058;178612057;178611954	chr2:179476785;179476784;179476681
N2A	14217	42874;42875;42876	chr2:178612058;178612057;178611954	chr2:179476785;179476784;179476681
N2B	7720	23383;23384;23385	chr2:178612058;178612057;178611954	chr2:179476785;179476784;179476681
Novex-1	7845	23758;23759;23760	chr2:178612058;178612057;178611954	chr2:179476785;179476784;179476681
Novex-2	7912	23959;23960;23961	chr2:178612058;178612057;178611954	chr2:179476785;179476784;179476681
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-10
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.262
• Predicted PPI site: N

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
R/K	None	None	0.543	N	0.226	0.187	0.263140351381	gnomAD-4.0.0	6.86944E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01157E-07	0	0
R/T	rs1363740118	None	0.998	N	0.697	0.331	0.410734915765	gnomAD-4.0.0	6.86944E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01157E-07	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
R/A	0.6772	likely_pathogenic	0.5983	pathogenic	-1.255	Destabilizing	0.992	D	0.533	neutral	None	None	None	None	N
R/C	0.2578	likely_benign	0.1912	benign	-1.256	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
R/D	0.8888	likely_pathogenic	0.8589	pathogenic	-0.298	Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	N
R/E	0.7147	likely_pathogenic	0.6492	pathogenic	-0.163	Destabilizing	0.992	D	0.437	neutral	None	None	None	None	N
R/F	0.8294	likely_pathogenic	0.7622	pathogenic	-1.011	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
R/G	0.3831	ambiguous	0.2967	benign	-1.575	Destabilizing	0.994	D	0.639	neutral	N	0.3887394	None	None	N
R/H	0.1491	likely_benign	0.1199	benign	-1.635	Destabilizing	1.0	D	0.577	neutral	None	None	None	None	N
R/I	0.6629	likely_pathogenic	0.6468	pathogenic	-0.377	Destabilizing	0.999	D	0.739	prob.delet.	N	0.484196667	None	None	N
R/K	0.1462	likely_benign	0.1128	benign	-1.263	Destabilizing	0.543	D	0.226	neutral	N	0.434093168	None	None	N
R/L	0.5718	likely_pathogenic	0.4926	ambiguous	-0.377	Destabilizing	0.996	D	0.639	neutral	None	None	None	None	N
R/M	0.5826	likely_pathogenic	0.5064	ambiguous	-0.641	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
R/N	0.709	likely_pathogenic	0.6501	pathogenic	-0.684	Destabilizing	0.999	D	0.572	neutral	None	None	None	None	N
R/P	0.9868	likely_pathogenic	0.9799	pathogenic	-0.651	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
R/Q	0.1789	likely_benign	0.1435	benign	-0.879	Destabilizing	0.998	D	0.559	neutral	None	None	None	None	N
R/S	0.6708	likely_pathogenic	0.592	pathogenic	-1.593	Destabilizing	0.989	D	0.633	neutral	N	0.41181798	None	None	N
R/T	0.5206	ambiguous	0.466	ambiguous	-1.269	Destabilizing	0.998	D	0.697	prob.neutral	N	0.475108175	None	None	N
R/V	0.7192	likely_pathogenic	0.6773	pathogenic	-0.651	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
R/W	0.4569	ambiguous	0.3741	ambiguous	-0.542	Destabilizing	1.0	D	0.634	neutral	None	None	None	None	N
R/Y	0.6028	likely_pathogenic	0.5241	ambiguous	-0.291	Destabilizing	1.0	D	0.728	prob.delet.	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.