TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16918	50977;50978;50979	chr2:178611477;178611476;178611475	chr2:179476204;179476203;179476202
N2AB	15277	46054;46055;46056	chr2:178611477;178611476;178611475	chr2:179476204;179476203;179476202
N2A	14350	43273;43274;43275	chr2:178611477;178611476;178611475	chr2:179476204;179476203;179476202
N2B	7853	23782;23783;23784	chr2:178611477;178611476;178611475	chr2:179476204;179476203;179476202
Novex-1	7978	24157;24158;24159	chr2:178611477;178611476;178611475	chr2:179476204;179476203;179476202
Novex-2	8045	24358;24359;24360	chr2:178611477;178611476;178611475	chr2:179476204;179476203;179476202
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-11
• Domain position: 67
• Structural Position: 97
• Q(SASA): 0.1088
• 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
V/A	rs765405714	-2.026	0.104	D	0.694	0.321	0.45349784317	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/A	rs765405714	-2.026	0.104	D	0.694	0.321	0.45349784317	gnomAD-4.0.0	1.59293E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43312E-05	0
V/G	None	None	0.667	D	0.855	0.454	0.655021911717	gnomAD-4.0.0	1.59293E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8613E-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
V/A	0.6596	likely_pathogenic	0.7657	pathogenic	-1.804	Destabilizing	0.104	N	0.694	prob.neutral	D	0.539615967	None	None	N
V/C	0.8873	likely_pathogenic	0.9428	pathogenic	-1.267	Destabilizing	0.968	D	0.826	deleterious	None	None	None	None	N
V/D	0.9742	likely_pathogenic	0.982	pathogenic	-1.764	Destabilizing	0.667	D	0.888	deleterious	D	0.581234271	None	None	N
V/E	0.9517	likely_pathogenic	0.9645	pathogenic	-1.679	Destabilizing	0.726	D	0.85	deleterious	None	None	None	None	N
V/F	0.5634	ambiguous	0.5874	pathogenic	-1.246	Destabilizing	0.002	N	0.641	neutral	D	0.53812432	None	None	N
V/G	0.7972	likely_pathogenic	0.8701	pathogenic	-2.221	Highly Destabilizing	0.667	D	0.855	deleterious	D	0.582490523	None	None	N
V/H	0.9831	likely_pathogenic	0.9891	pathogenic	-1.769	Destabilizing	0.968	D	0.891	deleterious	None	None	None	None	N
V/I	0.0807	likely_benign	0.0737	benign	-0.716	Destabilizing	None	N	0.357	neutral	N	0.46823939	None	None	N
V/K	0.9647	likely_pathogenic	0.9764	pathogenic	-1.56	Destabilizing	0.726	D	0.85	deleterious	None	None	None	None	N
V/L	0.3625	ambiguous	0.3837	ambiguous	-0.716	Destabilizing	0.009	N	0.566	neutral	N	0.31884379	None	None	N
V/M	0.3935	ambiguous	0.4111	ambiguous	-0.576	Destabilizing	0.567	D	0.735	prob.delet.	None	None	None	None	N
V/N	0.9262	likely_pathogenic	0.9476	pathogenic	-1.517	Destabilizing	0.89	D	0.886	deleterious	None	None	None	None	N
V/P	0.9423	likely_pathogenic	0.9594	pathogenic	-1.045	Destabilizing	0.89	D	0.859	deleterious	None	None	None	None	N
V/Q	0.9539	likely_pathogenic	0.9688	pathogenic	-1.567	Destabilizing	0.89	D	0.867	deleterious	None	None	None	None	N
V/R	0.9457	likely_pathogenic	0.965	pathogenic	-1.118	Destabilizing	0.726	D	0.883	deleterious	None	None	None	None	N
V/S	0.8518	likely_pathogenic	0.906	pathogenic	-2.115	Highly Destabilizing	0.726	D	0.828	deleterious	None	None	None	None	N
V/T	0.6564	likely_pathogenic	0.7664	pathogenic	-1.901	Destabilizing	0.272	N	0.727	prob.delet.	None	None	None	None	N
V/W	0.9816	likely_pathogenic	0.9882	pathogenic	-1.551	Destabilizing	0.968	D	0.877	deleterious	None	None	None	None	N
V/Y	0.9419	likely_pathogenic	0.959	pathogenic	-1.223	Destabilizing	0.396	N	0.807	deleterious	None	None	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.