TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26078	78457;78458;78459	chr2:178567900;178567899;178567898	chr2:179432627;179432626;179432625
N2AB	24437	73534;73535;73536	chr2:178567900;178567899;178567898	chr2:179432627;179432626;179432625
N2A	23510	70753;70754;70755	chr2:178567900;178567899;178567898	chr2:179432627;179432626;179432625
N2B	17013	51262;51263;51264	chr2:178567900;178567899;178567898	chr2:179432627;179432626;179432625
Novex-1	17138	51637;51638;51639	chr2:178567900;178567899;178567898	chr2:179432627;179432626;179432625
Novex-2	17205	51838;51839;51840	chr2:178567900;178567899;178567898	chr2:179432627;179432626;179432625
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-77
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.4251
• 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/N	rs1706533541	None	0.986	N	0.705	0.231	0.223847106136	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/N	rs1706533541	None	0.986	N	0.705	0.231	0.223847106136	gnomAD-4.0.0	6.57531E-06	None	None	None	None	N	None	2.41313E-05	0	None	0	0	None	0	0	0	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	0.716	likely_pathogenic	0.7838	pathogenic	0.023	Stabilizing	0.963	D	0.684	prob.delet.	None	None	None	None	N
K/C	0.8948	likely_pathogenic	0.9157	pathogenic	-0.18	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
K/D	0.902	likely_pathogenic	0.9247	pathogenic	0.092	Stabilizing	0.995	D	0.697	prob.delet.	None	None	None	None	N
K/E	0.5708	likely_pathogenic	0.6433	pathogenic	0.08	Stabilizing	0.952	D	0.691	prob.delet.	N	0.475298454	None	None	N
K/F	0.9594	likely_pathogenic	0.9695	pathogenic	-0.295	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/G	0.7889	likely_pathogenic	0.8454	pathogenic	-0.139	Destabilizing	0.995	D	0.69	prob.delet.	None	None	None	None	N
K/H	0.614	likely_pathogenic	0.6551	pathogenic	-0.408	Destabilizing	0.999	D	0.725	deleterious	None	None	None	None	N
K/I	0.7744	likely_pathogenic	0.8242	pathogenic	0.363	Stabilizing	0.995	D	0.773	deleterious	None	None	None	None	N
K/L	0.7408	likely_pathogenic	0.7847	pathogenic	0.363	Stabilizing	0.989	D	0.69	prob.delet.	None	None	None	None	N
K/M	0.6772	likely_pathogenic	0.7389	pathogenic	0.236	Stabilizing	0.999	D	0.731	deleterious	N	0.474478975	None	None	N
K/N	0.8302	likely_pathogenic	0.8669	pathogenic	0.321	Stabilizing	0.986	D	0.705	prob.delet.	N	0.47697051	None	None	N
K/P	0.782	likely_pathogenic	0.8466	pathogenic	0.276	Stabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
K/Q	0.3316	likely_benign	0.4012	ambiguous	0.112	Stabilizing	0.986	D	0.7	prob.delet.	N	0.505816149	None	None	N
K/R	0.0994	likely_benign	0.1067	benign	0.075	Stabilizing	0.125	N	0.463	neutral	N	0.507952377	None	None	N
K/S	0.81	likely_pathogenic	0.8616	pathogenic	-0.168	Destabilizing	0.963	D	0.709	prob.delet.	None	None	None	None	N
K/T	0.6332	likely_pathogenic	0.7114	pathogenic	-0.043	Destabilizing	0.993	D	0.681	prob.neutral	N	0.515513067	None	None	N
K/V	0.7037	likely_pathogenic	0.76	pathogenic	0.276	Stabilizing	0.995	D	0.744	deleterious	None	None	None	None	N
K/W	0.9337	likely_pathogenic	0.9487	pathogenic	-0.317	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
K/Y	0.8941	likely_pathogenic	0.9165	pathogenic	0.054	Stabilizing	0.998	D	0.799	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.