TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19962	60109;60110;60111	chr2:178592020;178592019;178592018	chr2:179456747;179456746;179456745
N2AB	18321	55186;55187;55188	chr2:178592020;178592019;178592018	chr2:179456747;179456746;179456745
N2A	17394	52405;52406;52407	chr2:178592020;178592019;178592018	chr2:179456747;179456746;179456745
N2B	10897	32914;32915;32916	chr2:178592020;178592019;178592018	chr2:179456747;179456746;179456745
Novex-1	11022	33289;33290;33291	chr2:178592020;178592019;178592018	chr2:179456747;179456746;179456745
Novex-2	11089	33490;33491;33492	chr2:178592020;178592019;178592018	chr2:179456747;179456746;179456745
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-32
• Domain position: 86
• Structural Position: 120
• Q(SASA): 0.3896
• 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/L	rs2050323196	None	0.64	N	0.501	0.386	0.27132560031	gnomAD-4.0.0	6.16102E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.09722E-06	0	0
F/S	rs878939618	None	0.984	N	0.626	0.325	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
F/S	rs878939618	None	0.984	N	0.626	0.325	None	gnomAD-4.0.0	1.31491E-05	None	None	None	None	N	None	4.82509E-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
F/A	0.676	likely_pathogenic	0.6714	pathogenic	-2.618	Highly Destabilizing	0.919	D	0.553	neutral	None	None	None	None	N
F/C	0.4485	ambiguous	0.4733	ambiguous	-1.113	Destabilizing	0.999	D	0.699	prob.neutral	N	0.483215161	None	None	N
F/D	0.8997	likely_pathogenic	0.8902	pathogenic	-2.991	Highly Destabilizing	0.996	D	0.699	prob.neutral	None	None	None	None	N
F/E	0.94	likely_pathogenic	0.9373	pathogenic	-2.829	Highly Destabilizing	0.988	D	0.675	prob.neutral	None	None	None	None	N
F/G	0.8886	likely_pathogenic	0.8766	pathogenic	-2.978	Highly Destabilizing	0.988	D	0.65	neutral	None	None	None	None	N
F/H	0.6539	likely_pathogenic	0.6653	pathogenic	-1.437	Destabilizing	0.976	D	0.657	neutral	None	None	None	None	N
F/I	0.6508	likely_pathogenic	0.677	pathogenic	-1.448	Destabilizing	0.896	D	0.499	neutral	N	0.481947714	None	None	N
F/K	0.9653	likely_pathogenic	0.9643	pathogenic	-1.747	Destabilizing	0.988	D	0.681	prob.neutral	None	None	None	None	N
F/L	0.9338	likely_pathogenic	0.9321	pathogenic	-1.448	Destabilizing	0.64	D	0.501	neutral	N	0.469412866	None	None	N
F/M	0.7809	likely_pathogenic	0.775	pathogenic	-0.922	Destabilizing	0.996	D	0.593	neutral	None	None	None	None	N
F/N	0.7932	likely_pathogenic	0.8033	pathogenic	-2.139	Highly Destabilizing	0.988	D	0.702	prob.neutral	None	None	None	None	N
F/P	0.8319	likely_pathogenic	0.855	pathogenic	-1.846	Destabilizing	0.996	D	0.715	prob.delet.	None	None	None	None	N
F/Q	0.9218	likely_pathogenic	0.9206	pathogenic	-2.189	Highly Destabilizing	0.996	D	0.709	prob.delet.	None	None	None	None	N
F/R	0.9285	likely_pathogenic	0.9236	pathogenic	-1.143	Destabilizing	0.988	D	0.707	prob.neutral	None	None	None	None	N
F/S	0.5977	likely_pathogenic	0.58	pathogenic	-2.654	Highly Destabilizing	0.984	D	0.626	neutral	N	0.481187245	None	None	N
F/T	0.8153	likely_pathogenic	0.82	pathogenic	-2.408	Highly Destabilizing	0.988	D	0.628	neutral	None	None	None	None	N
F/V	0.5555	ambiguous	0.5695	pathogenic	-1.846	Destabilizing	0.896	D	0.494	neutral	N	0.481440735	None	None	N
F/W	0.4711	ambiguous	0.4208	ambiguous	-0.524	Destabilizing	0.988	D	0.606	neutral	None	None	None	None	N
F/Y	0.1256	likely_benign	0.1269	benign	-0.798	Destabilizing	0.004	N	0.246	neutral	N	0.45327253	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.