TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27082	81469;81470;81471	chr2:178564888;178564887;178564886	chr2:179429615;179429614;179429613
N2AB	25441	76546;76547;76548	chr2:178564888;178564887;178564886	chr2:179429615;179429614;179429613
N2A	24514	73765;73766;73767	chr2:178564888;178564887;178564886	chr2:179429615;179429614;179429613
N2B	18017	54274;54275;54276	chr2:178564888;178564887;178564886	chr2:179429615;179429614;179429613
Novex-1	18142	54649;54650;54651	chr2:178564888;178564887;178564886	chr2:179429615;179429614;179429613
Novex-2	18209	54850;54851;54852	chr2:178564888;178564887;178564886	chr2:179429615;179429614;179429613
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-85
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.3402
• 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
T/I	rs368265185	0.097	0.968	N	0.605	0.326	None	gnomAD-2.1.1	8.11E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
T/I	rs368265185	0.097	0.968	N	0.605	0.326	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs368265185	0.097	0.968	N	0.605	0.326	None	gnomAD-4.0.0	1.36456E-05	None	None	None	None	N	None	2.67458E-05	0	None	0	0	None	0	0	1.69578E-05	0	0
T/K	rs368265185	None	0.896	N	0.577	0.265	0.389750110748	gnomAD-4.0.0	6.84878E-07	None	None	None	None	N	None	2.99976E-05	0	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
T/A	0.0828	likely_benign	0.0783	benign	-0.694	Destabilizing	0.011	N	0.153	neutral	N	0.503186849	None	None	N
T/C	0.3369	likely_benign	0.2931	benign	-0.437	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
T/D	0.3666	ambiguous	0.3565	ambiguous	0.445	Stabilizing	0.976	D	0.603	neutral	None	None	None	None	N
T/E	0.3004	likely_benign	0.2855	benign	0.463	Stabilizing	0.919	D	0.579	neutral	None	None	None	None	N
T/F	0.2271	likely_benign	0.2048	benign	-0.836	Destabilizing	0.988	D	0.719	prob.delet.	None	None	None	None	N
T/G	0.2305	likely_benign	0.2132	benign	-0.941	Destabilizing	0.851	D	0.615	neutral	None	None	None	None	N
T/H	0.2682	likely_benign	0.245	benign	-1.031	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
T/I	0.1385	likely_benign	0.1305	benign	-0.131	Destabilizing	0.968	D	0.605	neutral	N	0.490988343	None	None	N
T/K	0.2369	likely_benign	0.2236	benign	-0.329	Destabilizing	0.896	D	0.577	neutral	N	0.511035541	None	None	N
T/L	0.0927	likely_benign	0.0882	benign	-0.131	Destabilizing	0.919	D	0.578	neutral	None	None	None	None	N
T/M	0.1033	likely_benign	0.0961	benign	-0.126	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
T/N	0.1272	likely_benign	0.1235	benign	-0.375	Destabilizing	0.976	D	0.542	neutral	None	None	None	None	N
T/P	0.2557	likely_benign	0.3091	benign	-0.286	Destabilizing	0.984	D	0.646	neutral	N	0.473854454	None	None	N
T/Q	0.2519	likely_benign	0.2251	benign	-0.429	Destabilizing	0.988	D	0.671	neutral	None	None	None	None	N
T/R	0.2257	likely_benign	0.2078	benign	-0.164	Destabilizing	0.968	D	0.659	neutral	N	0.472080028	None	None	N
T/S	0.1026	likely_benign	0.0947	benign	-0.727	Destabilizing	0.103	N	0.16	neutral	N	0.429590381	None	None	N
T/V	0.1057	likely_benign	0.0996	benign	-0.286	Destabilizing	0.851	D	0.505	neutral	None	None	None	None	N
T/W	0.6501	likely_pathogenic	0.6098	pathogenic	-0.805	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
T/Y	0.2735	likely_benign	0.249	benign	-0.523	Destabilizing	0.996	D	0.713	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.