TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18635	56128;56129;56130	chr2:178601001;178601000;178600999	chr2:179465728;179465727;179465726
N2AB	16994	51205;51206;51207	chr2:178601001;178601000;178600999	chr2:179465728;179465727;179465726
N2A	16067	48424;48425;48426	chr2:178601001;178601000;178600999	chr2:179465728;179465727;179465726
N2B	9570	28933;28934;28935	chr2:178601001;178601000;178600999	chr2:179465728;179465727;179465726
Novex-1	9695	29308;29309;29310	chr2:178601001;178601000;178600999	chr2:179465728;179465727;179465726
Novex-2	9762	29509;29510;29511	chr2:178601001;178601000;178600999	chr2:179465728;179465727;179465726
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-23
• Domain position: 57
• Structural Position: 69
• Q(SASA): 0.1534
• 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
N/K	None	None	1.0	N	0.733	0.354	0.165133752707	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	1.01626E-03	None	0	0	None	0	0	0	0	0
N/S	None	None	0.999	N	0.587	0.273	0.231231049324	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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
N/A	0.8036	likely_pathogenic	0.8305	pathogenic	-0.966	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
N/C	0.6424	likely_pathogenic	0.633	pathogenic	-0.066	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
N/D	0.7982	likely_pathogenic	0.836	pathogenic	-0.521	Destabilizing	0.999	D	0.625	neutral	N	0.514075847	None	None	N
N/E	0.9627	likely_pathogenic	0.9716	pathogenic	-0.384	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
N/F	0.975	likely_pathogenic	0.9838	pathogenic	-0.668	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
N/G	0.7338	likely_pathogenic	0.7586	pathogenic	-1.337	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
N/H	0.6074	likely_pathogenic	0.6763	pathogenic	-0.966	Destabilizing	1.0	D	0.763	deleterious	N	0.497164954	None	None	N
N/I	0.8727	likely_pathogenic	0.9129	pathogenic	-0.004	Destabilizing	1.0	D	0.797	deleterious	N	0.474459884	None	None	N
N/K	0.9721	likely_pathogenic	0.9832	pathogenic	-0.171	Destabilizing	1.0	D	0.733	prob.delet.	N	0.468850797	None	None	N
N/L	0.8467	likely_pathogenic	0.8801	pathogenic	-0.004	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
N/M	0.9026	likely_pathogenic	0.9227	pathogenic	0.366	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
N/P	0.9234	likely_pathogenic	0.946	pathogenic	-0.295	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
N/Q	0.915	likely_pathogenic	0.9325	pathogenic	-0.76	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
N/R	0.952	likely_pathogenic	0.9675	pathogenic	-0.273	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
N/S	0.1809	likely_benign	0.162	benign	-0.95	Destabilizing	0.999	D	0.587	neutral	N	0.499951756	None	None	N
N/T	0.526	ambiguous	0.5776	pathogenic	-0.6	Destabilizing	0.999	D	0.688	prob.neutral	N	0.495391298	None	None	N
N/V	0.8061	likely_pathogenic	0.8532	pathogenic	-0.295	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
N/W	0.9893	likely_pathogenic	0.9919	pathogenic	-0.411	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
N/Y	0.8673	likely_pathogenic	0.9043	pathogenic	-0.185	Destabilizing	1.0	D	0.781	deleterious	N	0.496068876	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.