TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17557	52894;52895;52896	chr2:178608214;178608213;178608212	chr2:179472941;179472940;179472939
N2AB	15916	47971;47972;47973	chr2:178608214;178608213;178608212	chr2:179472941;179472940;179472939
N2A	14989	45190;45191;45192	chr2:178608214;178608213;178608212	chr2:179472941;179472940;179472939
N2B	8492	25699;25700;25701	chr2:178608214;178608213;178608212	chr2:179472941;179472940;179472939
Novex-1	8617	26074;26075;26076	chr2:178608214;178608213;178608212	chr2:179472941;179472940;179472939
Novex-2	8684	26275;26276;26277	chr2:178608214;178608213;178608212	chr2:179472941;179472940;179472939
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-15
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.5576
• 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
P/S	rs986749140	None	0.651	N	0.524	0.124	0.19670166235	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/S	rs986749140	None	0.651	N	0.524	0.124	0.19670166235	gnomAD-4.0.0	1.86965E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.55337E-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
P/A	0.0792	likely_benign	0.0745	benign	-1.233	Destabilizing	0.278	N	0.453	neutral	N	0.454792683	None	None	I
P/C	0.5078	ambiguous	0.4115	ambiguous	-0.742	Destabilizing	0.995	D	0.8	deleterious	None	None	None	None	I
P/D	0.4292	ambiguous	0.3652	ambiguous	-1.01	Destabilizing	0.946	D	0.517	neutral	None	None	None	None	I
P/E	0.217	likely_benign	0.1958	benign	-1.082	Destabilizing	0.946	D	0.507	neutral	None	None	None	None	I
P/F	0.386	ambiguous	0.3045	benign	-1.16	Destabilizing	0.946	D	0.782	deleterious	None	None	None	None	I
P/G	0.3575	ambiguous	0.3048	benign	-1.466	Destabilizing	0.008	N	0.428	neutral	None	None	None	None	I
P/H	0.2335	likely_benign	0.1991	benign	-0.928	Destabilizing	0.995	D	0.712	prob.delet.	None	None	None	None	I
P/I	0.1637	likely_benign	0.1385	benign	-0.726	Destabilizing	0.071	N	0.529	neutral	None	None	None	None	I
P/K	0.2975	likely_benign	0.2688	benign	-0.966	Destabilizing	0.946	D	0.514	neutral	None	None	None	None	I
P/L	0.0794	likely_benign	0.0726	benign	-0.726	Destabilizing	0.483	N	0.597	neutral	N	0.466433828	None	None	I
P/M	0.2037	likely_benign	0.1858	benign	-0.455	Destabilizing	0.946	D	0.708	prob.delet.	None	None	None	None	I
P/N	0.3405	ambiguous	0.2988	benign	-0.659	Destabilizing	0.946	D	0.722	deleterious	None	None	None	None	I
P/Q	0.1497	likely_benign	0.142	benign	-0.937	Destabilizing	0.976	D	0.597	neutral	N	0.466105754	None	None	I
P/R	0.2486	likely_benign	0.2144	benign	-0.33	Destabilizing	0.976	D	0.709	prob.delet.	N	0.479824413	None	None	I
P/S	0.1304	likely_benign	0.118	benign	-1.108	Destabilizing	0.651	D	0.524	neutral	N	0.448538714	None	None	I
P/T	0.1178	likely_benign	0.1046	benign	-1.082	Destabilizing	0.651	D	0.527	neutral	N	0.479304338	None	None	I
P/V	0.1242	likely_benign	0.1099	benign	-0.86	Destabilizing	0.008	N	0.492	neutral	None	None	None	None	I
P/W	0.6718	likely_pathogenic	0.559	ambiguous	-1.246	Destabilizing	0.995	D	0.761	deleterious	None	None	None	None	I
P/Y	0.4051	ambiguous	0.3206	benign	-0.983	Destabilizing	0.982	D	0.797	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.