TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18651	56176;56177;56178	chr2:178600953;178600952;178600951	chr2:179465680;179465679;179465678
N2AB	17010	51253;51254;51255	chr2:178600953;178600952;178600951	chr2:179465680;179465679;179465678
N2A	16083	48472;48473;48474	chr2:178600953;178600952;178600951	chr2:179465680;179465679;179465678
N2B	9586	28981;28982;28983	chr2:178600953;178600952;178600951	chr2:179465680;179465679;179465678
Novex-1	9711	29356;29357;29358	chr2:178600953;178600952;178600951	chr2:179465680;179465679;179465678
Novex-2	9778	29557;29558;29559	chr2:178600953;178600952;178600951	chr2:179465680;179465679;179465678
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-23
• Domain position: 73
• Structural Position: 99
• Q(SASA): 0.4201
• 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
E/G	rs876658067	-1.164	0.014	N	0.279	0.268	0.331365685468	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
E/G	rs876658067	-1.164	0.014	N	0.279	0.268	0.331365685468	gnomAD-4.0.0	8.214E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19837E-06	0	6.62888E-05
E/K	None	None	0.822	N	0.574	0.304	0.370240404367	gnomAD-4.0.0	1.59289E-06	None	None	None	None	N	None	5.66829E-05	0	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
E/A	0.1428	likely_benign	0.1338	benign	-0.533	Destabilizing	0.698	D	0.432	neutral	N	0.465479755	None	None	N
E/C	0.8676	likely_pathogenic	0.8372	pathogenic	-0.198	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
E/D	0.293	likely_benign	0.2512	benign	-0.53	Destabilizing	0.822	D	0.49	neutral	N	0.480549497	None	None	N
E/F	0.8712	likely_pathogenic	0.8239	pathogenic	-0.312	Destabilizing	0.998	D	0.646	neutral	None	None	None	None	N
E/G	0.2812	likely_benign	0.2439	benign	-0.764	Destabilizing	0.014	N	0.279	neutral	N	0.490678035	None	None	N
E/H	0.6654	likely_pathogenic	0.6201	pathogenic	-0.166	Destabilizing	0.998	D	0.576	neutral	None	None	None	None	N
E/I	0.4555	ambiguous	0.3995	ambiguous	0.053	Stabilizing	0.978	D	0.659	neutral	None	None	None	None	N
E/K	0.2692	likely_benign	0.2578	benign	0.085	Stabilizing	0.822	D	0.574	neutral	N	0.472293837	None	None	N
E/L	0.5611	ambiguous	0.4774	ambiguous	0.053	Stabilizing	0.978	D	0.635	neutral	None	None	None	None	N
E/M	0.5647	likely_pathogenic	0.503	ambiguous	0.178	Stabilizing	0.998	D	0.599	neutral	None	None	None	None	N
E/N	0.4167	ambiguous	0.3699	ambiguous	-0.28	Destabilizing	0.956	D	0.604	neutral	None	None	None	None	N
E/P	0.3634	ambiguous	0.3525	ambiguous	-0.122	Destabilizing	0.993	D	0.543	neutral	None	None	None	None	N
E/Q	0.1799	likely_benign	0.1647	benign	-0.237	Destabilizing	0.99	D	0.654	neutral	N	0.513459771	None	None	N
E/R	0.4065	ambiguous	0.3966	ambiguous	0.343	Stabilizing	0.978	D	0.607	neutral	None	None	None	None	N
E/S	0.2425	likely_benign	0.2124	benign	-0.456	Destabilizing	0.86	D	0.55	neutral	None	None	None	None	N
E/T	0.2994	likely_benign	0.248	benign	-0.271	Destabilizing	0.978	D	0.517	neutral	None	None	None	None	N
E/V	0.2733	likely_benign	0.2389	benign	-0.122	Destabilizing	0.971	D	0.594	neutral	N	0.475447389	None	None	N
E/W	0.9622	likely_pathogenic	0.9421	pathogenic	-0.122	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
E/Y	0.8092	likely_pathogenic	0.7575	pathogenic	-0.068	Destabilizing	0.993	D	0.608	neutral	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.