TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31200	93823;93824;93825	chr2:178548028;178548027;178548026	chr2:179412755;179412754;179412753
N2AB	29559	88900;88901;88902	chr2:178548028;178548027;178548026	chr2:179412755;179412754;179412753
N2A	28632	86119;86120;86121	chr2:178548028;178548027;178548026	chr2:179412755;179412754;179412753
N2B	22135	66628;66629;66630	chr2:178548028;178548027;178548026	chr2:179412755;179412754;179412753
Novex-1	22260	67003;67004;67005	chr2:178548028;178548027;178548026	chr2:179412755;179412754;179412753
Novex-2	22327	67204;67205;67206	chr2:178548028;178548027;178548026	chr2:179412755;179412754;179412753
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-115
• Domain position: 88
• Structural Position: 123
• Q(SASA): 0.3164
• 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
A/G	None	None	0.988	N	0.482	0.31	0.353761421236	gnomAD-4.0.0	1.36839E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79889E-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
A/C	0.639	likely_pathogenic	0.652	pathogenic	-0.864	Destabilizing	1.0	D	0.657	prob.neutral	None	None	None	None	I
A/D	0.8686	likely_pathogenic	0.7737	pathogenic	-1.283	Destabilizing	0.997	D	0.679	prob.neutral	N	0.509800603	None	None	I
A/E	0.8599	likely_pathogenic	0.7687	pathogenic	-1.31	Destabilizing	0.997	D	0.725	deleterious	None	None	None	None	I
A/F	0.7704	likely_pathogenic	0.7059	pathogenic	-0.994	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	I
A/G	0.2603	likely_benign	0.2318	benign	-1.165	Destabilizing	0.988	D	0.482	neutral	N	0.465844922	None	None	I
A/H	0.9235	likely_pathogenic	0.8837	pathogenic	-1.471	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
A/I	0.4956	ambiguous	0.4419	ambiguous	-0.345	Destabilizing	0.995	D	0.689	prob.delet.	None	None	None	None	I
A/K	0.9576	likely_pathogenic	0.9156	pathogenic	-1.254	Destabilizing	0.997	D	0.715	prob.delet.	None	None	None	None	I
A/L	0.3818	ambiguous	0.3298	benign	-0.345	Destabilizing	0.982	D	0.545	neutral	None	None	None	None	I
A/M	0.4312	ambiguous	0.4026	ambiguous	-0.299	Destabilizing	1.0	D	0.707	prob.delet.	None	None	None	None	I
A/N	0.6743	likely_pathogenic	0.5939	pathogenic	-0.945	Destabilizing	0.997	D	0.792	deleterious	None	None	None	None	I
A/P	0.7011	likely_pathogenic	0.55	ambiguous	-0.49	Destabilizing	0.999	D	0.729	deleterious	N	0.433414546	None	None	I
A/Q	0.8618	likely_pathogenic	0.7937	pathogenic	-1.093	Destabilizing	0.999	D	0.707	prob.delet.	None	None	None	None	I
A/R	0.931	likely_pathogenic	0.8707	pathogenic	-0.958	Destabilizing	0.997	D	0.72	deleterious	None	None	None	None	I
A/S	0.1631	likely_benign	0.1574	benign	-1.257	Destabilizing	0.894	D	0.484	neutral	N	0.440612664	None	None	I
A/T	0.1442	likely_benign	0.1402	benign	-1.195	Destabilizing	0.188	N	0.217	neutral	N	0.414138139	None	None	I
A/V	0.2479	likely_benign	0.2178	benign	-0.49	Destabilizing	0.976	D	0.481	neutral	N	0.452059022	None	None	I
A/W	0.9669	likely_pathogenic	0.9431	pathogenic	-1.372	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
A/Y	0.8578	likely_pathogenic	0.8089	pathogenic	-0.966	Destabilizing	0.999	D	0.816	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.