TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31980	96163;96164;96165	chr2:178544291;178544290;178544289	chr2:179409018;179409017;179409016
N2AB	30339	91240;91241;91242	chr2:178544291;178544290;178544289	chr2:179409018;179409017;179409016
N2A	29412	88459;88460;88461	chr2:178544291;178544290;178544289	chr2:179409018;179409017;179409016
N2B	22915	68968;68969;68970	chr2:178544291;178544290;178544289	chr2:179409018;179409017;179409016
Novex-1	23040	69343;69344;69345	chr2:178544291;178544290;178544289	chr2:179409018;179409017;179409016
Novex-2	23107	69544;69545;69546	chr2:178544291;178544290;178544289	chr2:179409018;179409017;179409016
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: Fn3-121
• Domain position: 72
• Structural Position: 103
• Q(SASA): 0.3777
• 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	rs1315935878	-0.645	0.999	N	0.6	0.405	0.259272394797	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
K/E	rs1315935878	-0.645	0.999	N	0.6	0.405	0.259272394797	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85851E-06	0	0
K/N	None	None	1.0	N	0.735	0.306	0.143124449307	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2752	likely_benign	0.2897	benign	-0.863	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
K/C	0.4641	ambiguous	0.5151	ambiguous	-0.948	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/D	0.623	likely_pathogenic	0.6256	pathogenic	-0.534	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
K/E	0.1899	likely_benign	0.1893	benign	-0.363	Destabilizing	0.999	D	0.6	neutral	N	0.365925691	None	None	N
K/F	0.6506	likely_pathogenic	0.677	pathogenic	-0.311	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/G	0.3934	ambiguous	0.3986	ambiguous	-1.281	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
K/H	0.2688	likely_benign	0.2889	benign	-1.501	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
K/I	0.253	likely_benign	0.2699	benign	0.257	Stabilizing	1.0	D	0.813	deleterious	N	0.472037223	None	None	N
K/L	0.2784	likely_benign	0.3011	benign	0.257	Stabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
K/M	0.1757	likely_benign	0.1774	benign	0.022	Stabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
K/N	0.3575	ambiguous	0.3497	ambiguous	-0.974	Destabilizing	1.0	D	0.735	prob.delet.	N	0.461780157	None	None	N
K/P	0.4627	ambiguous	0.4908	ambiguous	-0.088	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
K/Q	0.1198	likely_benign	0.1226	benign	-0.926	Destabilizing	1.0	D	0.717	prob.delet.	N	0.445426625	None	None	N
K/R	0.0867	likely_benign	0.0887	benign	-0.854	Destabilizing	0.999	D	0.537	neutral	N	0.458606566	None	None	N
K/S	0.3441	ambiguous	0.3472	ambiguous	-1.624	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
K/T	0.1411	likely_benign	0.1432	benign	-1.228	Destabilizing	1.0	D	0.785	deleterious	N	0.407716386	None	None	N
K/V	0.2408	likely_benign	0.2589	benign	-0.088	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
K/W	0.6709	likely_pathogenic	0.6923	pathogenic	-0.204	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/Y	0.515	ambiguous	0.5352	ambiguous	0.086	Stabilizing	1.0	D	0.785	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.