TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35454	106585;106586;106587	chr2:178530255;178530254;178530253	chr2:179394982;179394981;179394980
N2AB	33813	101662;101663;101664	chr2:178530255;178530254;178530253	chr2:179394982;179394981;179394980
N2A	32886	98881;98882;98883	chr2:178530255;178530254;178530253	chr2:179394982;179394981;179394980
N2B	26389	79390;79391;79392	chr2:178530255;178530254;178530253	chr2:179394982;179394981;179394980
Novex-1	26514	79765;79766;79767	chr2:178530255;178530254;178530253	chr2:179394982;179394981;179394980
Novex-2	26581	79966;79967;79968	chr2:178530255;178530254;178530253	chr2:179394982;179394981;179394980
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-166
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1709
• 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
T/P	rs1476312387	None	0.995	N	0.717	0.253	0.326881540566	gnomAD-4.0.0	1.62059E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.90831E-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
T/A	0.1084	likely_benign	0.116	benign	-1.269	Destabilizing	0.798	D	0.57	neutral	N	0.461134291	None	None	N
T/C	0.5629	ambiguous	0.5563	ambiguous	-0.927	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
T/D	0.4265	ambiguous	0.4393	ambiguous	-0.796	Destabilizing	0.996	D	0.703	prob.neutral	None	None	None	None	N
T/E	0.2373	likely_benign	0.23	benign	-0.684	Destabilizing	0.996	D	0.692	prob.neutral	None	None	None	None	N
T/F	0.2171	likely_benign	0.22	benign	-1.261	Destabilizing	0.978	D	0.71	prob.delet.	None	None	None	None	N
T/G	0.3086	likely_benign	0.3333	benign	-1.605	Destabilizing	0.963	D	0.661	neutral	None	None	None	None	N
T/H	0.3136	likely_benign	0.3	benign	-1.809	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
T/I	0.2078	likely_benign	0.2031	benign	-0.42	Destabilizing	0.827	D	0.634	neutral	N	0.428291154	None	None	N
T/K	0.2264	likely_benign	0.2167	benign	-0.57	Destabilizing	0.951	D	0.664	neutral	N	0.418055517	None	None	N
T/L	0.0984	likely_benign	0.0995	benign	-0.42	Destabilizing	0.724	D	0.542	neutral	None	None	None	None	N
T/M	0.088	likely_benign	0.086	benign	-0.213	Destabilizing	0.331	N	0.405	neutral	None	None	None	None	N
T/N	0.1356	likely_benign	0.1386	benign	-0.932	Destabilizing	0.996	D	0.625	neutral	None	None	None	None	N
T/P	0.7392	likely_pathogenic	0.7804	pathogenic	-0.673	Destabilizing	0.995	D	0.717	prob.delet.	N	0.455376172	None	None	N
T/Q	0.2104	likely_benign	0.2046	benign	-0.942	Destabilizing	0.989	D	0.727	prob.delet.	None	None	None	None	N
T/R	0.1797	likely_benign	0.1723	benign	-0.576	Destabilizing	0.986	D	0.712	prob.delet.	N	0.384020302	None	None	N
T/S	0.1283	likely_benign	0.1331	benign	-1.275	Destabilizing	0.951	D	0.565	neutral	N	0.426848359	None	None	N
T/V	0.1783	likely_benign	0.1773	benign	-0.673	Destabilizing	0.724	D	0.577	neutral	None	None	None	None	N
T/W	0.5746	likely_pathogenic	0.5765	pathogenic	-1.208	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
T/Y	0.2776	likely_benign	0.2826	benign	-0.903	Destabilizing	0.996	D	0.72	prob.delet.	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.