TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28240	84943;84944;84945	chr2:178561414;178561413;178561412	chr2:179426141;179426140;179426139
N2AB	26599	80020;80021;80022	chr2:178561414;178561413;178561412	chr2:179426141;179426140;179426139
N2A	25672	77239;77240;77241	chr2:178561414;178561413;178561412	chr2:179426141;179426140;179426139
N2B	19175	57748;57749;57750	chr2:178561414;178561413;178561412	chr2:179426141;179426140;179426139
Novex-1	19300	58123;58124;58125	chr2:178561414;178561413;178561412	chr2:179426141;179426140;179426139
Novex-2	19367	58324;58325;58326	chr2:178561414;178561413;178561412	chr2:179426141;179426140;179426139
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-93
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.2786
• 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
C/Y	rs1703613576	None	0.99	N	0.753	0.346	0.552326942858	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
C/Y	rs1703613576	None	0.99	N	0.753	0.346	0.552326942858	gnomAD-4.0.0	6.57281E-06	None	None	None	None	I	None	2.41243E-05	0	None	0	0	None	0	0	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
C/A	0.2956	likely_benign	0.2842	benign	-1.397	Destabilizing	0.717	D	0.503	neutral	None	None	None	None	I
C/D	0.8914	likely_pathogenic	0.8967	pathogenic	0.312	Stabilizing	0.978	D	0.759	deleterious	None	None	None	None	I
C/E	0.9026	likely_pathogenic	0.8999	pathogenic	0.383	Stabilizing	0.956	D	0.766	deleterious	None	None	None	None	I
C/F	0.3051	likely_benign	0.2996	benign	-0.832	Destabilizing	0.99	D	0.755	deleterious	N	0.440513877	None	None	I
C/G	0.2251	likely_benign	0.2362	benign	-1.67	Destabilizing	0.942	D	0.712	prob.delet.	N	0.513992915	None	None	I
C/H	0.683	likely_pathogenic	0.6718	pathogenic	-1.624	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	I
C/I	0.5969	likely_pathogenic	0.5601	ambiguous	-0.719	Destabilizing	0.978	D	0.675	prob.neutral	None	None	None	None	I
C/K	0.8946	likely_pathogenic	0.8899	pathogenic	-0.538	Destabilizing	0.956	D	0.757	deleterious	None	None	None	None	I
C/L	0.579	likely_pathogenic	0.5669	pathogenic	-0.719	Destabilizing	0.86	D	0.53	neutral	None	None	None	None	I
C/M	0.6838	likely_pathogenic	0.6719	pathogenic	-0.077	Destabilizing	0.998	D	0.71	prob.delet.	None	None	None	None	I
C/N	0.6614	likely_pathogenic	0.6775	pathogenic	-0.408	Destabilizing	0.978	D	0.791	deleterious	None	None	None	None	I
C/P	0.2815	likely_benign	0.2654	benign	-0.919	Destabilizing	0.019	N	0.557	neutral	None	None	None	None	I
C/Q	0.743	likely_pathogenic	0.724	pathogenic	-0.35	Destabilizing	0.978	D	0.797	deleterious	None	None	None	None	I
C/R	0.6797	likely_pathogenic	0.669	pathogenic	-0.411	Destabilizing	0.97	D	0.796	deleterious	N	0.502525128	None	None	I
C/S	0.31	likely_benign	0.3237	benign	-0.989	Destabilizing	0.822	D	0.605	neutral	N	0.469759348	None	None	I
C/T	0.6013	likely_pathogenic	0.5982	pathogenic	-0.74	Destabilizing	0.86	D	0.618	neutral	None	None	None	None	I
C/V	0.4863	ambiguous	0.4544	ambiguous	-0.919	Destabilizing	0.926	D	0.597	neutral	None	None	None	None	I
C/W	0.6654	likely_pathogenic	0.6528	pathogenic	-0.784	Destabilizing	0.997	D	0.731	prob.delet.	N	0.46258266	None	None	I
C/Y	0.3971	ambiguous	0.3862	ambiguous	-0.758	Destabilizing	0.99	D	0.753	deleterious	N	0.441495311	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.