TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21087	63484;63485;63486	chr2:178588148;178588147;178588146	chr2:179452875;179452874;179452873
N2AB	19446	58561;58562;58563	chr2:178588148;178588147;178588146	chr2:179452875;179452874;179452873
N2A	18519	55780;55781;55782	chr2:178588148;178588147;178588146	chr2:179452875;179452874;179452873
N2B	12022	36289;36290;36291	chr2:178588148;178588147;178588146	chr2:179452875;179452874;179452873
Novex-1	12147	36664;36665;36666	chr2:178588148;178588147;178588146	chr2:179452875;179452874;179452873
Novex-2	12214	36865;36866;36867	chr2:178588148;178588147;178588146	chr2:179452875;179452874;179452873
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: Fn3-41
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.518
• 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	rs1395427495	-0.527	0.999	N	0.62	0.233	0.342631996419	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/R	rs1395427495	-0.527	0.999	N	0.62	0.233	0.342631996419	gnomAD-4.0.0	6.57523E-06	None	None	None	None	I	None	2.41196E-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	0.4065	ambiguous	0.4399	ambiguous	-0.151	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	I
K/C	0.7498	likely_pathogenic	0.7431	pathogenic	-0.423	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
K/D	0.6507	likely_pathogenic	0.6772	pathogenic	0.004	Stabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
K/E	0.2905	likely_benign	0.3335	benign	0.063	Stabilizing	0.999	D	0.653	neutral	N	0.511630187	None	None	I
K/F	0.7741	likely_pathogenic	0.8136	pathogenic	-0.213	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	I
K/G	0.6259	likely_pathogenic	0.6369	pathogenic	-0.399	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
K/H	0.3991	ambiguous	0.4191	ambiguous	-0.576	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
K/I	0.3603	ambiguous	0.4075	ambiguous	0.442	Stabilizing	1.0	D	0.814	deleterious	N	0.486345941	None	None	I
K/L	0.3841	ambiguous	0.4227	ambiguous	0.442	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
K/M	0.269	likely_benign	0.3112	benign	0.033	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
K/N	0.5031	ambiguous	0.5585	ambiguous	-0.062	Destabilizing	1.0	D	0.753	deleterious	N	0.509730115	None	None	I
K/P	0.4095	ambiguous	0.4026	ambiguous	0.273	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
K/Q	0.1751	likely_benign	0.1911	benign	-0.108	Destabilizing	1.0	D	0.739	prob.delet.	N	0.52128982	None	None	I
K/R	0.1068	likely_benign	0.1034	benign	-0.141	Destabilizing	0.999	D	0.62	neutral	N	0.450197726	None	None	I
K/S	0.4982	ambiguous	0.5397	ambiguous	-0.548	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
K/T	0.2516	likely_benign	0.291	benign	-0.313	Destabilizing	1.0	D	0.791	deleterious	N	0.467988196	None	None	I
K/V	0.344	ambiguous	0.3849	ambiguous	0.273	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
K/W	0.8228	likely_pathogenic	0.8321	pathogenic	-0.243	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
K/Y	0.6744	likely_pathogenic	0.6849	pathogenic	0.099	Stabilizing	1.0	D	0.817	deleterious	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.