TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18027	54304;54305;54306	chr2:178605098;178605097;178605096	chr2:179469825;179469824;179469823
N2AB	16386	49381;49382;49383	chr2:178605098;178605097;178605096	chr2:179469825;179469824;179469823
N2A	15459	46600;46601;46602	chr2:178605098;178605097;178605096	chr2:179469825;179469824;179469823
N2B	8962	27109;27110;27111	chr2:178605098;178605097;178605096	chr2:179469825;179469824;179469823
Novex-1	9087	27484;27485;27486	chr2:178605098;178605097;178605096	chr2:179469825;179469824;179469823
Novex-2	9154	27685;27686;27687	chr2:178605098;178605097;178605096	chr2:179469825;179469824;179469823
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-114
• Domain position: 60
• Structural Position: 135
• Q(SASA): 0.0978
• 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	rs374256705	-2.069	0.961	N	0.749	0.195	None	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
K/E	rs374256705	-2.069	0.961	N	0.749	0.195	None	gnomAD-4.0.0	1.59331E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86228E-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
K/A	0.3668	ambiguous	0.3647	ambiguous	-0.405	Destabilizing	0.931	D	0.767	deleterious	None	None	None	None	N
K/C	0.6195	likely_pathogenic	0.5866	pathogenic	-0.631	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
K/D	0.7239	likely_pathogenic	0.7223	pathogenic	-0.84	Destabilizing	0.985	D	0.798	deleterious	None	None	None	None	N
K/E	0.2451	likely_benign	0.2365	benign	-0.759	Destabilizing	0.961	D	0.749	deleterious	N	0.461658019	None	None	N
K/F	0.6622	likely_pathogenic	0.6333	pathogenic	-0.306	Destabilizing	0.996	D	0.819	deleterious	None	None	None	None	N
K/G	0.6044	likely_pathogenic	0.5871	pathogenic	-0.747	Destabilizing	0.092	N	0.531	neutral	None	None	None	None	N
K/H	0.2634	likely_benign	0.2511	benign	-1.218	Destabilizing	0.191	N	0.641	neutral	None	None	None	None	N
K/I	0.2679	likely_benign	0.2557	benign	0.472	Stabilizing	0.989	D	0.809	deleterious	N	0.436954362	None	None	N
K/L	0.3515	ambiguous	0.3369	benign	0.472	Stabilizing	0.97	D	0.771	deleterious	None	None	None	None	N
K/M	0.2326	likely_benign	0.2204	benign	0.483	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/N	0.4763	ambiguous	0.4682	ambiguous	-0.645	Destabilizing	0.961	D	0.765	deleterious	N	0.435684926	None	None	N
K/P	0.961	likely_pathogenic	0.955	pathogenic	0.209	Stabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
K/Q	0.1382	likely_benign	0.1335	benign	-0.826	Destabilizing	0.994	D	0.753	deleterious	N	0.467450628	None	None	N
K/R	0.086	likely_benign	0.0824	benign	-0.644	Destabilizing	0.961	D	0.729	prob.delet.	N	0.414597578	None	None	N
K/S	0.4291	ambiguous	0.4266	ambiguous	-1.14	Destabilizing	0.942	D	0.757	deleterious	None	None	None	None	N
K/T	0.1616	likely_benign	0.1591	benign	-0.875	Destabilizing	0.248	N	0.586	neutral	N	0.408767683	None	None	N
K/V	0.2343	likely_benign	0.2289	benign	0.209	Stabilizing	0.97	D	0.768	deleterious	None	None	None	None	N
K/W	0.7237	likely_pathogenic	0.6905	pathogenic	-0.26	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/Y	0.6016	likely_pathogenic	0.566	pathogenic	0.111	Stabilizing	0.991	D	0.771	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.