TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21016	63271;63272;63273	chr2:178588679;178588678;178588677	chr2:179453406;179453405;179453404
N2AB	19375	58348;58349;58350	chr2:178588679;178588678;178588677	chr2:179453406;179453405;179453404
N2A	18448	55567;55568;55569	chr2:178588679;178588678;178588677	chr2:179453406;179453405;179453404
N2B	11951	36076;36077;36078	chr2:178588679;178588678;178588677	chr2:179453406;179453405;179453404
Novex-1	12076	36451;36452;36453	chr2:178588679;178588678;178588677	chr2:179453406;179453405;179453404
Novex-2	12143	36652;36653;36654	chr2:178588679;178588678;178588677	chr2:179453406;179453405;179453404
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-40
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.6364
• 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
S/N	None	None	0.722	N	0.378	0.153	0.226586394389	gnomAD-4.0.0	6.84504E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99747E-07	0	0
S/T	rs1169239147	None	0.034	N	0.19	0.089	0.177238962908	gnomAD-4.0.0	2.73802E-06	None	None	None	None	I	None	0	8.95015E-05	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
S/A	0.0611	likely_benign	0.0685	benign	-0.236	Destabilizing	0.011	N	0.185	neutral	None	None	None	None	I
S/C	0.0952	likely_benign	0.0926	benign	-0.432	Destabilizing	0.986	D	0.389	neutral	N	0.47674129	None	None	I
S/D	0.352	ambiguous	0.3339	benign	0.375	Stabilizing	0.775	D	0.325	neutral	None	None	None	None	I
S/E	0.4159	ambiguous	0.3899	ambiguous	0.29	Stabilizing	0.775	D	0.331	neutral	None	None	None	None	I
S/F	0.138	likely_benign	0.1409	benign	-0.909	Destabilizing	0.961	D	0.456	neutral	None	None	None	None	I
S/G	0.0853	likely_benign	0.0847	benign	-0.316	Destabilizing	0.008	N	0.183	neutral	N	0.471767864	None	None	I
S/H	0.2509	likely_benign	0.2162	benign	-0.576	Destabilizing	0.996	D	0.36	neutral	None	None	None	None	I
S/I	0.1026	likely_benign	0.1015	benign	-0.158	Destabilizing	0.901	D	0.451	neutral	N	0.506651229	None	None	I
S/K	0.4964	ambiguous	0.4294	ambiguous	-0.305	Destabilizing	0.775	D	0.323	neutral	None	None	None	None	I
S/L	0.0767	likely_benign	0.0814	benign	-0.158	Destabilizing	0.633	D	0.425	neutral	None	None	None	None	I
S/M	0.1026	likely_benign	0.1086	benign	-0.267	Destabilizing	0.996	D	0.359	neutral	None	None	None	None	I
S/N	0.091	likely_benign	0.0857	benign	-0.17	Destabilizing	0.722	D	0.378	neutral	N	0.476328322	None	None	I
S/P	0.5765	likely_pathogenic	0.5608	ambiguous	-0.157	Destabilizing	0.961	D	0.372	neutral	None	None	None	None	I
S/Q	0.3351	likely_benign	0.3072	benign	-0.325	Destabilizing	0.961	D	0.327	neutral	None	None	None	None	I
S/R	0.4953	ambiguous	0.4082	ambiguous	-0.082	Destabilizing	0.901	D	0.363	neutral	N	0.45352882	None	None	I
S/T	0.0543	likely_benign	0.056	benign	-0.271	Destabilizing	0.034	N	0.19	neutral	N	0.452123311	None	None	I
S/V	0.095	likely_benign	0.0998	benign	-0.157	Destabilizing	0.633	D	0.413	neutral	None	None	None	None	I
S/W	0.3143	likely_benign	0.2976	benign	-0.989	Destabilizing	0.996	D	0.599	neutral	None	None	None	None	I
S/Y	0.1387	likely_benign	0.1283	benign	-0.662	Destabilizing	0.987	D	0.457	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.