TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29725	89398;89399;89400	chr2:178553938;178553937;178553936	chr2:179418665;179418664;179418663
N2AB	28084	84475;84476;84477	chr2:178553938;178553937;178553936	chr2:179418665;179418664;179418663
N2A	27157	81694;81695;81696	chr2:178553938;178553937;178553936	chr2:179418665;179418664;179418663
N2B	20660	62203;62204;62205	chr2:178553938;178553937;178553936	chr2:179418665;179418664;179418663
Novex-1	20785	62578;62579;62580	chr2:178553938;178553937;178553936	chr2:179418665;179418664;179418663
Novex-2	20852	62779;62780;62781	chr2:178553938;178553937;178553936	chr2:179418665;179418664;179418663
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-104
• Domain position: 93
• Structural Position: 126
• Q(SASA): 0.0924
• 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
F/S	rs1284407579	-3.342	0.791	N	0.635	0.205	0.69386598177	gnomAD-2.1.1	4.16E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.43E-05	None	0	0	0
F/S	rs1284407579	-3.342	0.791	N	0.635	0.205	0.69386598177	gnomAD-4.0.0	1.6182E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.45964E-05	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
F/A	0.554	ambiguous	0.5586	ambiguous	-2.082	Highly Destabilizing	0.712	D	0.645	neutral	None	None	None	None	N
F/C	0.319	likely_benign	0.2667	benign	-0.882	Destabilizing	0.993	D	0.624	neutral	N	0.458739852	None	None	N
F/D	0.7299	likely_pathogenic	0.7454	pathogenic	-0.335	Destabilizing	0.982	D	0.741	deleterious	None	None	None	None	N
F/E	0.8221	likely_pathogenic	0.8356	pathogenic	-0.277	Destabilizing	0.946	D	0.724	deleterious	None	None	None	None	N
F/G	0.7342	likely_pathogenic	0.7174	pathogenic	-2.383	Highly Destabilizing	0.834	D	0.701	prob.delet.	None	None	None	None	N
F/H	0.5434	ambiguous	0.5506	ambiguous	-0.62	Destabilizing	0.897	D	0.658	prob.neutral	None	None	None	None	N
F/I	0.3277	likely_benign	0.2955	benign	-1.198	Destabilizing	0.483	N	0.654	prob.neutral	N	0.456659552	None	None	N
F/K	0.8637	likely_pathogenic	0.8801	pathogenic	-0.778	Destabilizing	0.946	D	0.723	deleterious	None	None	None	None	N
F/L	0.7939	likely_pathogenic	0.7986	pathogenic	-1.198	Destabilizing	0.002	N	0.187	neutral	N	0.436457638	None	None	N
F/M	0.547	ambiguous	0.5383	ambiguous	-0.87	Destabilizing	0.897	D	0.648	neutral	None	None	None	None	N
F/N	0.4539	ambiguous	0.4858	ambiguous	-0.687	Destabilizing	0.982	D	0.724	deleterious	None	None	None	None	N
F/P	0.7563	likely_pathogenic	0.772	pathogenic	-1.483	Destabilizing	0.982	D	0.721	deleterious	None	None	None	None	N
F/Q	0.8007	likely_pathogenic	0.8028	pathogenic	-0.828	Destabilizing	0.982	D	0.731	deleterious	None	None	None	None	N
F/R	0.7986	likely_pathogenic	0.8049	pathogenic	-0.108	Destabilizing	0.946	D	0.731	deleterious	None	None	None	None	N
F/S	0.4486	ambiguous	0.4387	ambiguous	-1.561	Destabilizing	0.791	D	0.635	neutral	N	0.429225021	None	None	N
F/T	0.5584	ambiguous	0.5531	ambiguous	-1.415	Destabilizing	0.834	D	0.64	neutral	None	None	None	None	N
F/V	0.3407	ambiguous	0.3028	benign	-1.483	Destabilizing	0.278	N	0.647	neutral	N	0.45213638	None	None	N
F/W	0.3804	ambiguous	0.3877	ambiguous	-0.408	Destabilizing	0.946	D	0.582	neutral	None	None	None	None	N
F/Y	0.0806	likely_benign	0.0796	benign	-0.558	Destabilizing	0.002	N	0.185	neutral	N	0.390437347	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.