TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5204	15835;15836;15837	chr2:178733779;178733778;178733777	chr2:179598506;179598505;179598504
N2AB	4887	14884;14885;14886	chr2:178733779;178733778;178733777	chr2:179598506;179598505;179598504
N2A	3960	12103;12104;12105	chr2:178733779;178733778;178733777	chr2:179598506;179598505;179598504
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-35
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.3617
• 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
G/D	rs1171039782	-0.382	0.001	N	0.308	0.258	0.0846915920261	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	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
G/A	0.1785	likely_benign	0.1866	benign	-0.342	Destabilizing	0.201	N	0.437	neutral	N	0.458226763	None	None	I
G/C	0.3088	likely_benign	0.3475	ambiguous	-0.768	Destabilizing	0.976	D	0.665	neutral	N	0.485880696	None	None	I
G/D	0.1047	likely_benign	0.1153	benign	-0.815	Destabilizing	0.001	N	0.308	neutral	N	0.325721669	None	None	I
G/E	0.1414	likely_benign	0.1378	benign	-0.966	Destabilizing	0.002	N	0.42	neutral	None	None	None	None	I
G/F	0.5886	likely_pathogenic	0.6535	pathogenic	-0.992	Destabilizing	0.982	D	0.659	neutral	None	None	None	None	I
G/H	0.3667	ambiguous	0.4135	ambiguous	-0.781	Destabilizing	0.947	D	0.579	neutral	None	None	None	None	I
G/I	0.4487	ambiguous	0.4859	ambiguous	-0.358	Destabilizing	0.826	D	0.666	neutral	None	None	None	None	I
G/K	0.4211	ambiguous	0.4537	ambiguous	-1.034	Destabilizing	0.539	D	0.509	neutral	None	None	None	None	I
G/L	0.4645	ambiguous	0.5214	ambiguous	-0.358	Destabilizing	0.7	D	0.655	neutral	None	None	None	None	I
G/M	0.5302	ambiguous	0.5645	pathogenic	-0.345	Destabilizing	0.982	D	0.661	neutral	None	None	None	None	I
G/N	0.1525	likely_benign	0.1677	benign	-0.563	Destabilizing	0.399	N	0.43	neutral	None	None	None	None	I
G/P	0.918	likely_pathogenic	0.9303	pathogenic	-0.317	Destabilizing	0.826	D	0.569	neutral	None	None	None	None	I
G/Q	0.2657	likely_benign	0.2877	benign	-0.855	Destabilizing	0.539	D	0.569	neutral	None	None	None	None	I
G/R	0.3348	likely_benign	0.363	ambiguous	-0.584	Destabilizing	0.468	N	0.567	neutral	N	0.450289726	None	None	I
G/S	0.1077	likely_benign	0.118	benign	-0.689	Destabilizing	0.201	N	0.425	neutral	N	0.456279581	None	None	I
G/T	0.2812	likely_benign	0.3049	benign	-0.777	Destabilizing	0.7	D	0.515	neutral	None	None	None	None	I
G/V	0.3256	likely_benign	0.363	ambiguous	-0.317	Destabilizing	0.638	D	0.649	neutral	N	0.458651893	None	None	I
G/W	0.4582	ambiguous	0.4985	ambiguous	-1.208	Destabilizing	0.982	D	0.61	neutral	None	None	None	None	I
G/Y	0.371	ambiguous	0.4312	ambiguous	-0.848	Destabilizing	0.982	D	0.658	neutral	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.