TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9519	28780;28781;28782	chr2:178709764;178709763;178709762	chr2:179574491;179574490;179574489
N2AB	9202	27829;27830;27831	chr2:178709764;178709763;178709762	chr2:179574491;179574490;179574489
N2A	8275	25048;25049;25050	chr2:178709764;178709763;178709762	chr2:179574491;179574490;179574489
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: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-81
• Domain position: 27
• Structural Position: 40
• Q(SASA): 0.3976
• 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
G/C	None	None	1.0	None	0.711	0.713	0.903793654709	gnomAD-4.0.0	1.59123E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85802E-06	0	0
G/D	rs1166241741	None	1.0	None	0.825	0.711	0.673404836468	gnomAD-4.0.0	1.59123E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85798E-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
G/A	0.6104	likely_pathogenic	0.6946	pathogenic	-0.189	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
G/C	0.9311	likely_pathogenic	0.9582	pathogenic	-0.825	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
G/D	0.985	likely_pathogenic	0.9916	pathogenic	-0.514	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/E	0.9882	likely_pathogenic	0.9929	pathogenic	-0.676	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/F	0.9914	likely_pathogenic	0.9933	pathogenic	-0.934	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
G/H	0.9954	likely_pathogenic	0.9973	pathogenic	-0.514	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
G/I	0.9795	likely_pathogenic	0.9877	pathogenic	-0.319	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
G/K	0.9955	likely_pathogenic	0.9977	pathogenic	-0.78	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/L	0.9841	likely_pathogenic	0.9902	pathogenic	-0.319	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
G/M	0.9926	likely_pathogenic	0.9952	pathogenic	-0.399	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I
G/N	0.9872	likely_pathogenic	0.9927	pathogenic	-0.394	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
G/P	0.9962	likely_pathogenic	0.997	pathogenic	-0.242	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
G/Q	0.9911	likely_pathogenic	0.9946	pathogenic	-0.673	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/R	0.9821	likely_pathogenic	0.9902	pathogenic	-0.367	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
G/S	0.6949	likely_pathogenic	0.7811	pathogenic	-0.533	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
G/T	0.9469	likely_pathogenic	0.9645	pathogenic	-0.625	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/V	0.9487	likely_pathogenic	0.967	pathogenic	-0.242	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
G/W	0.9882	likely_pathogenic	0.9925	pathogenic	-1.112	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
G/Y	0.9909	likely_pathogenic	0.9944	pathogenic	-0.745	Destabilizing	1.0	D	0.746	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.