TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32741	98446;98447;98448	chr2:178539844;178539843;178539842	chr2:179404571;179404570;179404569
N2AB	31100	93523;93524;93525	chr2:178539844;178539843;178539842	chr2:179404571;179404570;179404569
N2A	30173	90742;90743;90744	chr2:178539844;178539843;178539842	chr2:179404571;179404570;179404569
N2B	23676	71251;71252;71253	chr2:178539844;178539843;178539842	chr2:179404571;179404570;179404569
Novex-1	23801	71626;71627;71628	chr2:178539844;178539843;178539842	chr2:179404571;179404570;179404569
Novex-2	23868	71827;71828;71829	chr2:178539844;178539843;178539842	chr2:179404571;179404570;179404569
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-155
• Domain position: 34
• Structural Position: 51
• Q(SASA): 0.5398
• 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
E/K	rs1693522689	None	0.822	N	0.521	0.255	0.215869574891	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/K	rs1693522689	None	0.822	N	0.521	0.255	0.215869574891	gnomAD-4.0.0	2.56216E-06	None	None	None	None	N	None	0	1.69515E-05	None	0	0	None	0	0	2.39294E-06	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
E/A	0.1727	likely_benign	0.1815	benign	-0.581	Destabilizing	0.822	D	0.551	neutral	N	0.479450693	None	None	N
E/C	0.8219	likely_pathogenic	0.8298	pathogenic	0.038	Stabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	N
E/D	0.0979	likely_benign	0.0961	benign	-0.365	Destabilizing	0.002	N	0.218	neutral	N	0.385188164	None	None	N
E/F	0.8363	likely_pathogenic	0.8442	pathogenic	-0.502	Destabilizing	0.993	D	0.637	neutral	None	None	None	None	N
E/G	0.1268	likely_benign	0.1313	benign	-0.8	Destabilizing	0.822	D	0.579	neutral	N	0.460054069	None	None	N
E/H	0.6288	likely_pathogenic	0.6579	pathogenic	-0.503	Destabilizing	0.993	D	0.441	neutral	None	None	None	None	N
E/I	0.656	likely_pathogenic	0.6825	pathogenic	-0.03	Destabilizing	0.978	D	0.635	neutral	None	None	None	None	N
E/K	0.3135	likely_benign	0.3341	benign	0.266	Stabilizing	0.822	D	0.521	neutral	N	0.482336282	None	None	N
E/L	0.5583	ambiguous	0.5782	pathogenic	-0.03	Destabilizing	0.978	D	0.617	neutral	None	None	None	None	N
E/M	0.601	likely_pathogenic	0.6205	pathogenic	0.289	Stabilizing	0.998	D	0.607	neutral	None	None	None	None	N
E/N	0.2174	likely_benign	0.2286	benign	-0.058	Destabilizing	0.754	D	0.485	neutral	None	None	None	None	N
E/P	0.8852	likely_pathogenic	0.9197	pathogenic	-0.194	Destabilizing	0.978	D	0.468	neutral	None	None	None	None	N
E/Q	0.2163	likely_benign	0.2289	benign	-0.018	Destabilizing	0.904	D	0.457	neutral	N	0.452565016	None	None	N
E/R	0.4223	ambiguous	0.4433	ambiguous	0.358	Stabilizing	0.978	D	0.447	neutral	None	None	None	None	N
E/S	0.2358	likely_benign	0.2465	benign	-0.241	Destabilizing	0.86	D	0.506	neutral	None	None	None	None	N
E/T	0.3924	ambiguous	0.4238	ambiguous	-0.058	Destabilizing	0.86	D	0.503	neutral	None	None	None	None	N
E/V	0.4111	ambiguous	0.4388	ambiguous	-0.194	Destabilizing	0.97	D	0.542	neutral	N	0.502231552	None	None	N
E/W	0.9244	likely_pathogenic	0.9346	pathogenic	-0.336	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
E/Y	0.6661	likely_pathogenic	0.696	pathogenic	-0.256	Destabilizing	0.993	D	0.596	neutral	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.