TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29557	88894;88895;88896	chr2:178554678;178554677;178554676	chr2:179419405;179419404;179419403
N2AB	27916	83971;83972;83973	chr2:178554678;178554677;178554676	chr2:179419405;179419404;179419403
N2A	26989	81190;81191;81192	chr2:178554678;178554677;178554676	chr2:179419405;179419404;179419403
N2B	20492	61699;61700;61701	chr2:178554678;178554677;178554676	chr2:179419405;179419404;179419403
Novex-1	20617	62074;62075;62076	chr2:178554678;178554677;178554676	chr2:179419405;179419404;179419403
Novex-2	20684	62275;62276;62277	chr2:178554678;178554677;178554676	chr2:179419405;179419404;179419403
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-103
• Domain position: 25
• Structural Position: 26
• Q(SASA): 0.3703
• 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
P/H	None	None	1.0	N	0.868	0.472	0.602320007227	gnomAD-4.0.0	1.591E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85778E-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	0.093	likely_benign	0.0892	benign	-1.535	Destabilizing	1.0	D	0.814	deleterious	N	0.484563803	None	None	N
P/C	0.5174	ambiguous	0.4892	ambiguous	-1.003	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
P/D	0.5669	likely_pathogenic	0.5259	ambiguous	-1.583	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
P/E	0.2657	likely_benign	0.2384	benign	-1.533	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
P/F	0.5471	ambiguous	0.53	ambiguous	-1.128	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
P/G	0.4462	ambiguous	0.4158	ambiguous	-1.867	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/H	0.2528	likely_benign	0.2294	benign	-1.289	Destabilizing	1.0	D	0.868	deleterious	N	0.500876387	None	None	N
P/I	0.3031	likely_benign	0.2735	benign	-0.695	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/K	0.2688	likely_benign	0.2434	benign	-1.323	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
P/L	0.1243	likely_benign	0.1189	benign	-0.695	Destabilizing	1.0	D	0.885	deleterious	N	0.485227667	None	None	N
P/M	0.2895	likely_benign	0.273	benign	-0.655	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/N	0.4575	ambiguous	0.4173	ambiguous	-1.191	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
P/Q	0.1518	likely_benign	0.1393	benign	-1.289	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
P/R	0.2008	likely_benign	0.1833	benign	-0.855	Destabilizing	1.0	D	0.902	deleterious	N	0.498305493	None	None	N
P/S	0.1792	likely_benign	0.1637	benign	-1.657	Destabilizing	1.0	D	0.863	deleterious	N	0.488506124	None	None	N
P/T	0.1634	likely_benign	0.1471	benign	-1.487	Destabilizing	1.0	D	0.87	deleterious	N	0.493532553	None	None	N
P/V	0.2142	likely_benign	0.1964	benign	-0.944	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
P/W	0.7198	likely_pathogenic	0.7111	pathogenic	-1.323	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/Y	0.5031	ambiguous	0.4797	ambiguous	-1.033	Destabilizing	1.0	D	0.895	deleterious	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.