TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21952	66079;66080;66081	chr2:178582949;178582948;178582947	chr2:179447676;179447675;179447674
N2AB	20311	61156;61157;61158	chr2:178582949;178582948;178582947	chr2:179447676;179447675;179447674
N2A	19384	58375;58376;58377	chr2:178582949;178582948;178582947	chr2:179447676;179447675;179447674
N2B	12887	38884;38885;38886	chr2:178582949;178582948;178582947	chr2:179447676;179447675;179447674
Novex-1	13012	39259;39260;39261	chr2:178582949;178582948;178582947	chr2:179447676;179447675;179447674
Novex-2	13079	39460;39461;39462	chr2:178582949;178582948;178582947	chr2:179447676;179447675;179447674
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-125
• Domain position: 87
• Structural Position: 175
• Q(SASA): 0.619
• 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
K/E	rs2048118319	None	0.811	N	0.601	0.276	0.233785782151	gnomAD-4.0.0	5.55821E-06	None	None	None	None	N	None	0	0	None	0	5.77301E-05	None	0	0	3.27255E-06	0	0
K/I	rs371740766	None	0.968	N	0.74	0.443	None	gnomAD-4.0.0	1.45816E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.87469E-06	0	0
K/R	None	None	0.811	N	0.555	0.157	0.367042808489	gnomAD-4.0.0	7.29079E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.37346E-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
K/A	0.6409	likely_pathogenic	0.5053	ambiguous	-0.736	Destabilizing	0.919	D	0.599	neutral	None	None	None	None	N
K/C	0.7727	likely_pathogenic	0.6592	pathogenic	-0.799	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
K/D	0.8683	likely_pathogenic	0.8009	pathogenic	-0.026	Destabilizing	0.976	D	0.597	neutral	None	None	None	None	N
K/E	0.4118	ambiguous	0.3224	benign	0.116	Stabilizing	0.811	D	0.601	neutral	N	0.475454035	None	None	N
K/F	0.8959	likely_pathogenic	0.8335	pathogenic	-0.319	Destabilizing	0.996	D	0.746	deleterious	None	None	None	None	N
K/G	0.8699	likely_pathogenic	0.7982	pathogenic	-1.125	Destabilizing	0.919	D	0.613	neutral	None	None	None	None	N
K/H	0.3705	ambiguous	0.289	benign	-1.342	Destabilizing	0.997	D	0.618	neutral	None	None	None	None	N
K/I	0.4244	ambiguous	0.3377	benign	0.286	Stabilizing	0.968	D	0.74	deleterious	N	0.474590031	None	None	N
K/L	0.4666	ambiguous	0.3356	benign	0.286	Stabilizing	0.919	D	0.62	neutral	None	None	None	None	N
K/M	0.2938	likely_benign	0.2187	benign	0.082	Stabilizing	0.997	D	0.616	neutral	None	None	None	None	N
K/N	0.6601	likely_pathogenic	0.5659	pathogenic	-0.596	Destabilizing	0.968	D	0.547	neutral	N	0.460775371	None	None	N
K/P	0.9906	likely_pathogenic	0.9814	pathogenic	-0.025	Destabilizing	0.988	D	0.631	neutral	None	None	None	None	N
K/Q	0.1855	likely_benign	0.1353	benign	-0.613	Destabilizing	0.211	N	0.339	neutral	N	0.475280677	None	None	N
K/R	0.1008	likely_benign	0.0982	benign	-0.621	Destabilizing	0.811	D	0.555	neutral	N	0.472165801	None	None	N
K/S	0.7095	likely_pathogenic	0.5864	pathogenic	-1.337	Destabilizing	0.851	D	0.582	neutral	None	None	None	None	N
K/T	0.2621	likely_benign	0.1882	benign	-0.974	Destabilizing	0.103	N	0.398	neutral	N	0.445939205	None	None	N
K/V	0.4063	ambiguous	0.3274	benign	-0.025	Destabilizing	0.976	D	0.608	neutral	None	None	None	None	N
K/W	0.8732	likely_pathogenic	0.8058	pathogenic	-0.161	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
K/Y	0.7933	likely_pathogenic	0.6988	pathogenic	0.127	Stabilizing	0.996	D	0.737	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.