TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32287	97084;97085;97086	chr2:178543114;178543113;178543112	chr2:179407841;179407840;179407839
N2AB	30646	92161;92162;92163	chr2:178543114;178543113;178543112	chr2:179407841;179407840;179407839
N2A	29719	89380;89381;89382	chr2:178543114;178543113;178543112	chr2:179407841;179407840;179407839
N2B	23222	69889;69890;69891	chr2:178543114;178543113;178543112	chr2:179407841;179407840;179407839
Novex-1	23347	70264;70265;70266	chr2:178543114;178543113;178543112	chr2:179407841;179407840;179407839
Novex-2	23414	70465;70466;70467	chr2:178543114;178543113;178543112	chr2:179407841;179407840;179407839
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: Fn3-123
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.4962
• 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
E/K	None	None	0.999	N	0.682	0.4	0.355865052028	gnomAD-4.0.0	1.60118E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.88309E-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	0.1802	likely_benign	0.1741	benign	-0.572	Destabilizing	0.999	D	0.743	deleterious	N	0.489870835	None	None	I
E/C	0.8856	likely_pathogenic	0.8929	pathogenic	-0.287	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
E/D	0.1312	likely_benign	0.1181	benign	-0.494	Destabilizing	0.999	D	0.584	neutral	N	0.461473513	None	None	I
E/F	0.7803	likely_pathogenic	0.7854	pathogenic	-0.291	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
E/G	0.238	likely_benign	0.2341	benign	-0.785	Destabilizing	1.0	D	0.742	deleterious	N	0.478761844	None	None	I
E/H	0.5721	likely_pathogenic	0.5812	pathogenic	0.035	Stabilizing	1.0	D	0.631	neutral	None	None	None	None	I
E/I	0.416	ambiguous	0.3975	ambiguous	-0.033	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
E/K	0.208	likely_benign	0.2079	benign	0.133	Stabilizing	0.999	D	0.682	prob.neutral	N	0.462030873	None	None	I
E/L	0.4031	ambiguous	0.3955	ambiguous	-0.033	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
E/M	0.5102	ambiguous	0.4952	ambiguous	0.043	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
E/N	0.3379	likely_benign	0.3189	benign	-0.333	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
E/P	0.3941	ambiguous	0.4193	ambiguous	-0.193	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
E/Q	0.1747	likely_benign	0.1752	benign	-0.284	Destabilizing	1.0	D	0.687	prob.neutral	N	0.50970739	None	None	I
E/R	0.3533	ambiguous	0.3746	ambiguous	0.454	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
E/S	0.2447	likely_benign	0.2415	benign	-0.482	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	I
E/T	0.3111	likely_benign	0.3031	benign	-0.302	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
E/V	0.2493	likely_benign	0.2384	benign	-0.193	Destabilizing	1.0	D	0.788	deleterious	N	0.473383474	None	None	I
E/W	0.9263	likely_pathogenic	0.9297	pathogenic	-0.068	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
E/Y	0.6598	likely_pathogenic	0.6566	pathogenic	-0.039	Destabilizing	1.0	D	0.755	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.