TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26425	79498;79499;79500	chr2:178566859;178566858;178566857	chr2:179431586;179431585;179431584
N2AB	24784	74575;74576;74577	chr2:178566859;178566858;178566857	chr2:179431586;179431585;179431584
N2A	23857	71794;71795;71796	chr2:178566859;178566858;178566857	chr2:179431586;179431585;179431584
N2B	17360	52303;52304;52305	chr2:178566859;178566858;178566857	chr2:179431586;179431585;179431584
Novex-1	17485	52678;52679;52680	chr2:178566859;178566858;178566857	chr2:179431586;179431585;179431584
Novex-2	17552	52879;52880;52881	chr2:178566859;178566858;178566857	chr2:179431586;179431585;179431584
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: Fn3-80
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1337
• 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	rs1706063163	None	0.41	N	0.669	0.446	0.28297238246	gnomAD-4.0.0	3.49016E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49775E-05	0	1.65706E-05
K/I	rs1359744760	-0.056	0.908	N	0.849	0.354	0.418718287753	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/I	rs1359744760	-0.056	0.908	N	0.849	0.354	0.418718287753	gnomAD-4.0.0	2.05305E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.47818E-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
K/A	0.9906	likely_pathogenic	0.9894	pathogenic	-1.428	Destabilizing	0.648	D	0.675	prob.neutral	None	None	None	None	N
K/C	0.9617	likely_pathogenic	0.9592	pathogenic	-1.493	Destabilizing	0.993	D	0.822	deleterious	None	None	None	None	N
K/D	0.9988	likely_pathogenic	0.9987	pathogenic	-2.366	Highly Destabilizing	0.866	D	0.808	deleterious	None	None	None	None	N
K/E	0.9831	likely_pathogenic	0.9824	pathogenic	-2.036	Highly Destabilizing	0.41	N	0.669	neutral	N	0.511046788	None	None	N
K/F	0.9941	likely_pathogenic	0.9936	pathogenic	-0.615	Destabilizing	0.98	D	0.841	deleterious	None	None	None	None	N
K/G	0.9894	likely_pathogenic	0.989	pathogenic	-1.92	Destabilizing	0.866	D	0.769	deleterious	None	None	None	None	N
K/H	0.8883	likely_pathogenic	0.8959	pathogenic	-1.643	Destabilizing	0.98	D	0.813	deleterious	None	None	None	None	N
K/I	0.9752	likely_pathogenic	0.9719	pathogenic	-0.011	Destabilizing	0.908	D	0.849	deleterious	N	0.469518679	None	None	N
K/L	0.9406	likely_pathogenic	0.9358	pathogenic	-0.011	Destabilizing	0.866	D	0.769	deleterious	None	None	None	None	N
K/M	0.8819	likely_pathogenic	0.8776	pathogenic	-0.42	Destabilizing	0.993	D	0.805	deleterious	None	None	None	None	N
K/N	0.994	likely_pathogenic	0.9933	pathogenic	-2.129	Highly Destabilizing	0.83	D	0.811	deleterious	N	0.511046788	None	None	N
K/P	0.9994	likely_pathogenic	0.9995	pathogenic	-0.466	Destabilizing	0.929	D	0.82	deleterious	None	None	None	None	N
K/Q	0.788	likely_pathogenic	0.8141	pathogenic	-1.684	Destabilizing	0.83	D	0.808	deleterious	N	0.483396653	None	None	N
K/R	0.1175	likely_benign	0.13	benign	-1.044	Destabilizing	0.01	N	0.402	neutral	N	0.439154013	None	None	N
K/S	0.994	likely_pathogenic	0.9937	pathogenic	-2.55	Highly Destabilizing	0.648	D	0.715	prob.delet.	None	None	None	None	N
K/T	0.9782	likely_pathogenic	0.9778	pathogenic	-1.961	Destabilizing	0.83	D	0.784	deleterious	N	0.491675085	None	None	N
K/V	0.9628	likely_pathogenic	0.9579	pathogenic	-0.466	Destabilizing	0.866	D	0.802	deleterious	None	None	None	None	N
K/W	0.9865	likely_pathogenic	0.9879	pathogenic	-0.749	Destabilizing	0.993	D	0.791	deleterious	None	None	None	None	N
K/Y	0.9606	likely_pathogenic	0.9586	pathogenic	-0.395	Destabilizing	0.929	D	0.849	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.