TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32729	98410;98411;98412	chr2:178539880;178539879;178539878	chr2:179404607;179404606;179404605
N2AB	31088	93487;93488;93489	chr2:178539880;178539879;178539878	chr2:179404607;179404606;179404605
N2A	30161	90706;90707;90708	chr2:178539880;178539879;178539878	chr2:179404607;179404606;179404605
N2B	23664	71215;71216;71217	chr2:178539880;178539879;178539878	chr2:179404607;179404606;179404605
Novex-1	23789	71590;71591;71592	chr2:178539880;178539879;178539878	chr2:179404607;179404606;179404605
Novex-2	23856	71791;71792;71793	chr2:178539880;178539879;178539878	chr2:179404607;179404606;179404605
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-155
• Domain position: 22
• Structural Position: 38
• Q(SASA): 0.9694
• Predicted PPI site: I

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/R	rs1368497531	0.099	0.018	N	0.254	0.115	0.307332253619	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
K/R	rs1368497531	0.099	0.018	N	0.254	0.115	0.307332253619	gnomAD-4.0.0	1.3684E-06	None	None	None	None	I	None	0	2.23624E-05	None	0	2.5194E-05	None	0	0	0	0	0
K/T	rs1368497531	None	0.722	N	0.507	0.284	0.29132392195	gnomAD-4.0.0	1.3684E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79895E-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	0.5366	ambiguous	0.4803	ambiguous	-0.067	Destabilizing	0.775	D	0.477	neutral	None	None	None	None	I
K/C	0.7221	likely_pathogenic	0.6747	pathogenic	-0.689	Destabilizing	0.996	D	0.566	neutral	None	None	None	None	I
K/D	0.8721	likely_pathogenic	0.8492	pathogenic	-0.379	Destabilizing	0.961	D	0.488	neutral	None	None	None	None	I
K/E	0.3995	ambiguous	0.3632	ambiguous	-0.39	Destabilizing	0.722	D	0.449	neutral	N	0.457020203	None	None	I
K/F	0.8483	likely_pathogenic	0.8195	pathogenic	-0.447	Destabilizing	0.923	D	0.557	neutral	None	None	None	None	I
K/G	0.7209	likely_pathogenic	0.683	pathogenic	-0.172	Destabilizing	0.775	D	0.491	neutral	None	None	None	None	I
K/H	0.3589	ambiguous	0.3259	benign	-0.195	Destabilizing	0.989	D	0.511	neutral	None	None	None	None	I
K/I	0.4711	ambiguous	0.4341	ambiguous	0.126	Stabilizing	0.565	D	0.49	neutral	N	0.498869613	None	None	I
K/L	0.5644	likely_pathogenic	0.5191	ambiguous	0.126	Stabilizing	0.415	N	0.488	neutral	None	None	None	None	I
K/M	0.3678	ambiguous	0.3313	benign	-0.29	Destabilizing	0.415	N	0.44	neutral	None	None	None	None	I
K/N	0.6927	likely_pathogenic	0.6566	pathogenic	-0.257	Destabilizing	0.901	D	0.455	neutral	N	0.510086684	None	None	I
K/P	0.9768	likely_pathogenic	0.9804	pathogenic	0.083	Stabilizing	0.987	D	0.503	neutral	None	None	None	None	I
K/Q	0.2106	likely_benign	0.1892	benign	-0.359	Destabilizing	0.901	D	0.47	neutral	N	0.440341384	None	None	I
K/R	0.0859	likely_benign	0.0873	benign	-0.228	Destabilizing	0.018	N	0.254	neutral	N	0.457041633	None	None	I
K/S	0.6078	likely_pathogenic	0.557	ambiguous	-0.589	Destabilizing	0.775	D	0.466	neutral	None	None	None	None	I
K/T	0.2502	likely_benign	0.215	benign	-0.491	Destabilizing	0.722	D	0.507	neutral	N	0.422870344	None	None	I
K/V	0.4383	ambiguous	0.4002	ambiguous	0.083	Stabilizing	0.044	N	0.353	neutral	None	None	None	None	I
K/W	0.8117	likely_pathogenic	0.7876	pathogenic	-0.574	Destabilizing	0.996	D	0.607	neutral	None	None	None	None	I
K/Y	0.7634	likely_pathogenic	0.7354	pathogenic	-0.228	Destabilizing	0.987	D	0.552	neutral	None	None	None	None	I

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.