TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32712	98359;98360;98361	chr2:178539931;178539930;178539929	chr2:179404658;179404657;179404656
N2AB	31071	93436;93437;93438	chr2:178539931;178539930;178539929	chr2:179404658;179404657;179404656
N2A	30144	90655;90656;90657	chr2:178539931;178539930;178539929	chr2:179404658;179404657;179404656
N2B	23647	71164;71165;71166	chr2:178539931;178539930;178539929	chr2:179404658;179404657;179404656
Novex-1	23772	71539;71540;71541	chr2:178539931;178539930;178539929	chr2:179404658;179404657;179404656
Novex-2	23839	71740;71741;71742	chr2:178539931;178539930;178539929	chr2:179404658;179404657;179404656
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: Ig-155
• Domain position: 5
• Structural Position: 9
• Q(SASA): 0.638
• 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	rs1169770151	-0.021	0.117	N	0.385	0.044	0.0954503805726	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/D	rs1169770151	-0.021	0.117	N	0.385	0.044	0.0954503805726	gnomAD-4.0.0	5.47444E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.1967E-06	0	0
E/Q	None	None	0.997	N	0.679	0.304	0.151104730317	gnomAD-4.0.0	1.59164E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85907E-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	0.1657	likely_benign	0.1639	benign	-0.067	Destabilizing	0.977	D	0.707	prob.neutral	N	0.458768776	None	None	N
E/C	0.8306	likely_pathogenic	0.8198	pathogenic	-0.042	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
E/D	0.0921	likely_benign	0.0906	benign	-0.21	Destabilizing	0.117	N	0.385	neutral	N	0.371515151	None	None	N
E/F	0.7799	likely_pathogenic	0.7686	pathogenic	-0.064	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
E/G	0.1485	likely_benign	0.1519	benign	-0.204	Destabilizing	0.993	D	0.669	neutral	N	0.477354537	None	None	N
E/H	0.4552	ambiguous	0.4467	ambiguous	0.426	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
E/I	0.4981	ambiguous	0.4718	ambiguous	0.239	Stabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
E/K	0.1697	likely_benign	0.1766	benign	0.522	Stabilizing	0.977	D	0.677	prob.neutral	N	0.428328439	None	None	N
E/L	0.4996	ambiguous	0.4801	ambiguous	0.239	Stabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
E/M	0.5479	ambiguous	0.5255	ambiguous	0.117	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/N	0.2161	likely_benign	0.2116	benign	0.245	Stabilizing	0.99	D	0.734	prob.delet.	None	None	None	None	N
E/P	0.5592	ambiguous	0.5567	ambiguous	0.156	Stabilizing	0.998	D	0.732	prob.delet.	None	None	None	None	N
E/Q	0.17	likely_benign	0.1737	benign	0.266	Stabilizing	0.997	D	0.679	prob.neutral	N	0.409166675	None	None	N
E/R	0.2896	likely_benign	0.2952	benign	0.715	Stabilizing	0.998	D	0.747	deleterious	None	None	None	None	N
E/S	0.1936	likely_benign	0.194	benign	0.103	Stabilizing	0.983	D	0.697	prob.neutral	None	None	None	None	N
E/T	0.2311	likely_benign	0.2221	benign	0.223	Stabilizing	0.998	D	0.72	prob.delet.	None	None	None	None	N
E/V	0.297	likely_benign	0.2818	benign	0.156	Stabilizing	0.997	D	0.75	deleterious	N	0.488744967	None	None	N
E/W	0.8704	likely_pathogenic	0.8652	pathogenic	0.007	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/Y	0.6087	likely_pathogenic	0.5857	pathogenic	0.169	Stabilizing	1.0	D	0.757	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.