TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7733	23422;23423;23424	chr2:178720565;178720564;178720563	chr2:179585292;179585291;179585290
N2AB	7416	22471;22472;22473	chr2:178720565;178720564;178720563	chr2:179585292;179585291;179585290
N2A	6489	19690;19691;19692	chr2:178720565;178720564;178720563	chr2:179585292;179585291;179585290
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-62
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2625
• 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
V/A	None	None	0.999	D	0.653	0.848	0.820583082347	gnomAD-4.0.0	4.1063E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39781E-06	0	0
V/I	rs1238420893	None	0.434	N	0.294	0.262	0.581534369529	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
V/I	rs1238420893	None	0.434	N	0.294	0.262	0.581534369529	gnomAD-4.0.0	1.21793E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.32543E-05	0	3.40229E-05

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
V/A	0.5674	likely_pathogenic	0.5997	pathogenic	-1.5	Destabilizing	0.999	D	0.653	neutral	D	0.605427828	None	None	N
V/C	0.967	likely_pathogenic	0.9683	pathogenic	-1.082	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/D	0.971	likely_pathogenic	0.9763	pathogenic	-1.173	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/E	0.9465	likely_pathogenic	0.9581	pathogenic	-1.11	Destabilizing	1.0	D	0.876	deleterious	D	0.631974961	None	None	N
V/F	0.6148	likely_pathogenic	0.6234	pathogenic	-0.963	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/G	0.768	likely_pathogenic	0.7979	pathogenic	-1.893	Destabilizing	1.0	D	0.875	deleterious	D	0.6159556	None	None	N
V/H	0.9865	likely_pathogenic	0.9888	pathogenic	-1.439	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
V/I	0.0982	likely_benign	0.0973	benign	-0.495	Destabilizing	0.434	N	0.294	neutral	N	0.45672192	None	None	N
V/K	0.9657	likely_pathogenic	0.9737	pathogenic	-1.254	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/L	0.6026	likely_pathogenic	0.6263	pathogenic	-0.495	Destabilizing	0.922	D	0.628	neutral	D	0.548093878	None	None	N
V/M	0.4303	ambiguous	0.4519	ambiguous	-0.457	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
V/N	0.9338	likely_pathogenic	0.9467	pathogenic	-1.134	Destabilizing	0.999	D	0.884	deleterious	None	None	None	None	N
V/P	0.9546	likely_pathogenic	0.9614	pathogenic	-0.795	Destabilizing	0.999	D	0.876	deleterious	None	None	None	None	N
V/Q	0.9582	likely_pathogenic	0.9672	pathogenic	-1.186	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
V/R	0.9562	likely_pathogenic	0.9661	pathogenic	-0.874	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
V/S	0.8353	likely_pathogenic	0.8678	pathogenic	-1.751	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
V/T	0.5325	ambiguous	0.5877	pathogenic	-1.557	Destabilizing	0.997	D	0.759	deleterious	None	None	None	None	N
V/W	0.9859	likely_pathogenic	0.9866	pathogenic	-1.219	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/Y	0.9442	likely_pathogenic	0.9461	pathogenic	-0.895	Destabilizing	1.0	D	0.823	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.