TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31191	93796;93797;93798	chr2:178548055;178548054;178548053	chr2:179412782;179412781;179412780
N2AB	29550	88873;88874;88875	chr2:178548055;178548054;178548053	chr2:179412782;179412781;179412780
N2A	28623	86092;86093;86094	chr2:178548055;178548054;178548053	chr2:179412782;179412781;179412780
N2B	22126	66601;66602;66603	chr2:178548055;178548054;178548053	chr2:179412782;179412781;179412780
Novex-1	22251	66976;66977;66978	chr2:178548055;178548054;178548053	chr2:179412782;179412781;179412780
Novex-2	22318	67177;67178;67179	chr2:178548055;178548054;178548053	chr2:179412782;179412781;179412780
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-115
• Domain position: 79
• Structural Position: 113
• Q(SASA): 0.6774
• 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
D/E	rs965506398	0.051	0.928	N	0.354	0.13	0.0551355673512	gnomAD-2.1.1	8.03E-06	None	None	None	None	I	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
D/E	rs965506398	0.051	0.928	N	0.354	0.13	0.0551355673512	gnomAD-4.0.0	6.36422E-06	None	None	None	None	I	None	0	4.5731E-05	None	0	0	None	0	0	5.71576E-06	0	0
D/Y	None	None	0.999	N	0.634	0.273	0.542187413537	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.1827	likely_benign	0.1648	benign	-0.08	Destabilizing	0.978	D	0.527	neutral	N	0.425184639	None	None	I
D/C	0.7488	likely_pathogenic	0.7099	pathogenic	0.354	Stabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	I
D/E	0.1392	likely_benign	0.1373	benign	-0.172	Destabilizing	0.928	D	0.354	neutral	N	0.430649173	None	None	I
D/F	0.6789	likely_pathogenic	0.6278	pathogenic	-0.328	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	I
D/G	0.3035	likely_benign	0.2766	benign	-0.205	Destabilizing	0.865	D	0.571	neutral	N	0.468143195	None	None	I
D/H	0.367	ambiguous	0.306	benign	-0.138	Destabilizing	0.994	D	0.607	neutral	N	0.454662184	None	None	I
D/I	0.3989	ambiguous	0.3415	ambiguous	0.179	Stabilizing	0.992	D	0.65	neutral	None	None	None	None	I
D/K	0.4676	ambiguous	0.3877	ambiguous	0.628	Stabilizing	0.968	D	0.58	neutral	None	None	None	None	I
D/L	0.4379	ambiguous	0.375	ambiguous	0.179	Stabilizing	0.983	D	0.615	neutral	None	None	None	None	I
D/M	0.6216	likely_pathogenic	0.566	pathogenic	0.354	Stabilizing	0.999	D	0.669	neutral	None	None	None	None	I
D/N	0.1374	likely_benign	0.1114	benign	0.513	Stabilizing	0.085	N	0.439	neutral	N	0.475882818	None	None	I
D/P	0.8701	likely_pathogenic	0.8256	pathogenic	0.112	Stabilizing	0.992	D	0.619	neutral	None	None	None	None	I
D/Q	0.373	ambiguous	0.3258	benign	0.494	Stabilizing	0.983	D	0.639	neutral	None	None	None	None	I
D/R	0.5147	ambiguous	0.4267	ambiguous	0.616	Stabilizing	0.983	D	0.61	neutral	None	None	None	None	I
D/S	0.1708	likely_benign	0.149	benign	0.415	Stabilizing	0.895	D	0.56	neutral	None	None	None	None	I
D/T	0.2828	likely_benign	0.2506	benign	0.509	Stabilizing	0.983	D	0.581	neutral	None	None	None	None	I
D/V	0.2447	likely_benign	0.2153	benign	0.112	Stabilizing	0.989	D	0.616	neutral	N	0.454950185	None	None	I
D/W	0.933	likely_pathogenic	0.9076	pathogenic	-0.309	Destabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	I
D/Y	0.334	likely_benign	0.2851	benign	-0.108	Destabilizing	0.999	D	0.634	neutral	N	0.471648727	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.