TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19026	57301;57302;57303	chr2:178598541;178598540;178598539	chr2:179463268;179463267;179463266
N2AB	17385	52378;52379;52380	chr2:178598541;178598540;178598539	chr2:179463268;179463267;179463266
N2A	16458	49597;49598;49599	chr2:178598541;178598540;178598539	chr2:179463268;179463267;179463266
N2B	9961	30106;30107;30108	chr2:178598541;178598540;178598539	chr2:179463268;179463267;179463266
Novex-1	10086	30481;30482;30483	chr2:178598541;178598540;178598539	chr2:179463268;179463267;179463266
Novex-2	10153	30682;30683;30684	chr2:178598541;178598540;178598539	chr2:179463268;179463267;179463266
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: Fn3-26
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1217
• 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/D	None	None	0.999	N	0.654	0.21	0.30212335484	gnomAD-4.0.0	1.60275E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86666E-06	0	0
E/Q	rs794727393	None	1.0	D	0.762	0.294	0.282179105231	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07383E-04	0
E/Q	rs794727393	None	1.0	D	0.762	0.294	0.282179105231	gnomAD-4.0.0	4.35069E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	7.81355E-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
E/A	0.8563	likely_pathogenic	0.8596	pathogenic	-1.533	Destabilizing	0.999	D	0.687	prob.neutral	D	0.527949729	None	None	N
E/C	0.9685	likely_pathogenic	0.9721	pathogenic	-0.754	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/D	0.8361	likely_pathogenic	0.8552	pathogenic	-1.729	Destabilizing	0.999	D	0.654	neutral	N	0.47734672	None	None	N
E/F	0.9748	likely_pathogenic	0.982	pathogenic	-1.184	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/G	0.9164	likely_pathogenic	0.9165	pathogenic	-1.917	Destabilizing	1.0	D	0.745	deleterious	D	0.529724155	None	None	N
E/H	0.9623	likely_pathogenic	0.9678	pathogenic	-1.073	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/I	0.9543	likely_pathogenic	0.9583	pathogenic	-0.426	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/K	0.9495	likely_pathogenic	0.9543	pathogenic	-1.593	Destabilizing	0.999	D	0.68	prob.neutral	N	0.51154054	None	None	N
E/L	0.9589	likely_pathogenic	0.962	pathogenic	-0.426	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
E/M	0.9433	likely_pathogenic	0.9525	pathogenic	0.308	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/N	0.9738	likely_pathogenic	0.9793	pathogenic	-1.796	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/P	0.9993	likely_pathogenic	0.9992	pathogenic	-0.782	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/Q	0.6671	likely_pathogenic	0.6775	pathogenic	-1.519	Destabilizing	1.0	D	0.762	deleterious	D	0.523810051	None	None	N
E/R	0.9498	likely_pathogenic	0.9493	pathogenic	-1.386	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/S	0.8939	likely_pathogenic	0.9013	pathogenic	-2.415	Highly Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
E/T	0.9452	likely_pathogenic	0.9474	pathogenic	-2.055	Highly Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/V	0.9063	likely_pathogenic	0.9135	pathogenic	-0.782	Destabilizing	1.0	D	0.739	prob.delet.	D	0.528710197	None	None	N
E/W	0.9864	likely_pathogenic	0.989	pathogenic	-1.258	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/Y	0.9488	likely_pathogenic	0.9629	pathogenic	-1.003	Destabilizing	1.0	D	0.769	deleterious	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.