TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18654	56185;56186;56187	chr2:178600944;178600943;178600942	chr2:179465671;179465670;179465669
N2AB	17013	51262;51263;51264	chr2:178600944;178600943;178600942	chr2:179465671;179465670;179465669
N2A	16086	48481;48482;48483	chr2:178600944;178600943;178600942	chr2:179465671;179465670;179465669
N2B	9589	28990;28991;28992	chr2:178600944;178600943;178600942	chr2:179465671;179465670;179465669
Novex-1	9714	29365;29366;29367	chr2:178600944;178600943;178600942	chr2:179465671;179465670;179465669
Novex-2	9781	29566;29567;29568	chr2:178600944;178600943;178600942	chr2:179465671;179465670;179465669
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-23
• Domain position: 76
• Structural Position: 103
• Q(SASA): 0.2709
• 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/D	rs2053252489	None	0.977	N	0.482	0.236	0.26169431596	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs2053252489	None	0.977	N	0.482	0.236	0.26169431596	gnomAD-4.0.0	6.57869E-06	None	None	None	None	N	None	2.41418E-05	0	None	0	0	None	0	0	0	0	0
E/K	rs879244493	None	0.955	N	0.533	0.307	0.198526703765	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs879244493	None	0.955	N	0.533	0.307	0.198526703765	gnomAD-4.0.0	6.57981E-06	None	None	None	None	N	None	2.41429E-05	0	None	0	0	None	0	0	0	0	0
E/V	None	None	0.997	N	0.843	0.382	0.492134657179	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
E/A	0.1754	likely_benign	0.1688	benign	-0.947	Destabilizing	0.977	D	0.645	neutral	N	0.468788345	None	None	N
E/C	0.7704	likely_pathogenic	0.7749	pathogenic	-0.447	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
E/D	0.2412	likely_benign	0.1983	benign	-1.142	Destabilizing	0.977	D	0.482	neutral	N	0.513537129	None	None	N
E/F	0.7234	likely_pathogenic	0.7083	pathogenic	-0.245	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
E/G	0.2814	likely_benign	0.2496	benign	-1.389	Destabilizing	0.993	D	0.779	deleterious	N	0.4769551	None	None	N
E/H	0.4567	ambiguous	0.4395	ambiguous	-0.596	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	N
E/I	0.2457	likely_benign	0.2433	benign	0.291	Stabilizing	0.998	D	0.858	deleterious	None	None	None	None	N
E/K	0.1209	likely_benign	0.13	benign	-0.723	Destabilizing	0.955	D	0.533	neutral	N	0.47694161	None	None	N
E/L	0.3135	likely_benign	0.3192	benign	0.291	Stabilizing	0.995	D	0.845	deleterious	None	None	None	None	N
E/M	0.3305	likely_benign	0.3366	benign	0.9	Stabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
E/N	0.2889	likely_benign	0.2524	benign	-1.239	Destabilizing	0.995	D	0.723	prob.delet.	None	None	None	None	N
E/P	0.6777	likely_pathogenic	0.6415	pathogenic	-0.101	Destabilizing	0.998	D	0.851	deleterious	None	None	None	None	N
E/Q	0.1036	likely_benign	0.1043	benign	-1.008	Destabilizing	0.568	D	0.22	neutral	N	0.509688747	None	None	N
E/R	0.2122	likely_benign	0.222	benign	-0.545	Destabilizing	0.99	D	0.722	prob.delet.	None	None	None	None	N
E/S	0.2195	likely_benign	0.1995	benign	-1.729	Destabilizing	0.983	D	0.576	neutral	None	None	None	None	N
E/T	0.1746	likely_benign	0.1632	benign	-1.335	Destabilizing	0.995	D	0.807	deleterious	None	None	None	None	N
E/V	0.1678	likely_benign	0.1653	benign	-0.101	Destabilizing	0.997	D	0.843	deleterious	N	0.516193432	None	None	N
E/W	0.8829	likely_pathogenic	0.8734	pathogenic	-0.009	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/Y	0.6177	likely_pathogenic	0.5951	pathogenic	0.035	Stabilizing	0.999	D	0.855	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.