TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8579	25960;25961;25962	chr2:178715679;178715678;178715677	chr2:179580406;179580405;179580404
N2AB	8262	25009;25010;25011	chr2:178715679;178715678;178715677	chr2:179580406;179580405;179580404
N2A	7335	22228;22229;22230	chr2:178715679;178715678;178715677	chr2:179580406;179580405;179580404
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-71
• Domain position: 31
• Structural Position: 44
• Q(SASA): 0.0925
• 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
I/F	None	None	0.013	D	0.349	0.307	0.513280433867	gnomAD-4.0.0	6.84841E-07	None	None	None	None	I	None	2.98989E-05	0	None	0	0	None	0	0	0	0	0
I/V	None	None	0.035	D	0.387	0.158	0.556183318313	gnomAD-4.0.0	1.36968E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99977E-07	1.1629E-05	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
I/A	0.8812	likely_pathogenic	0.8723	pathogenic	-2.454	Highly Destabilizing	0.919	D	0.535	neutral	None	None	None	None	I
I/C	0.9536	likely_pathogenic	0.9475	pathogenic	-1.633	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	I
I/D	0.9823	likely_pathogenic	0.9819	pathogenic	-2.653	Highly Destabilizing	0.997	D	0.689	prob.neutral	None	None	None	None	I
I/E	0.9599	likely_pathogenic	0.9572	pathogenic	-2.502	Highly Destabilizing	0.995	D	0.683	prob.neutral	None	None	None	None	I
I/F	0.3921	ambiguous	0.4039	ambiguous	-1.555	Destabilizing	0.013	N	0.349	neutral	D	0.534443624	None	None	I
I/G	0.9578	likely_pathogenic	0.9545	pathogenic	-2.942	Highly Destabilizing	0.997	D	0.692	prob.neutral	None	None	None	None	I
I/H	0.9567	likely_pathogenic	0.9549	pathogenic	-2.384	Highly Destabilizing	0.998	D	0.633	neutral	None	None	None	None	I
I/K	0.9045	likely_pathogenic	0.9024	pathogenic	-1.873	Destabilizing	0.896	D	0.691	prob.neutral	None	None	None	None	I
I/L	0.231	likely_benign	0.2173	benign	-1.079	Destabilizing	None	N	0.103	neutral	N	0.475469891	None	None	I
I/M	0.1307	likely_benign	0.129	benign	-0.879	Destabilizing	0.811	D	0.596	neutral	N	0.485630331	None	None	I
I/N	0.8038	likely_pathogenic	0.7909	pathogenic	-1.982	Destabilizing	0.996	D	0.696	prob.neutral	N	0.518066633	None	None	I
I/P	0.8565	likely_pathogenic	0.8477	pathogenic	-1.515	Destabilizing	0.997	D	0.692	prob.neutral	None	None	None	None	I
I/Q	0.9228	likely_pathogenic	0.919	pathogenic	-1.971	Destabilizing	0.992	D	0.682	prob.neutral	None	None	None	None	I
I/R	0.8926	likely_pathogenic	0.8889	pathogenic	-1.446	Destabilizing	0.992	D	0.7	prob.neutral	None	None	None	None	I
I/S	0.8869	likely_pathogenic	0.883	pathogenic	-2.638	Highly Destabilizing	0.984	D	0.649	neutral	D	0.524746705	None	None	I
I/T	0.8692	likely_pathogenic	0.8626	pathogenic	-2.354	Highly Destabilizing	0.862	D	0.627	neutral	N	0.499455398	None	None	I
I/V	0.1879	likely_benign	0.1901	benign	-1.515	Destabilizing	0.035	N	0.387	neutral	D	0.533750191	None	None	I
I/W	0.9395	likely_pathogenic	0.94	pathogenic	-1.907	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	I
I/Y	0.8421	likely_pathogenic	0.8405	pathogenic	-1.643	Destabilizing	0.526	D	0.656	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.